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Because Ras signaling is frequently activated by major hepatocellular carcinoma etiological factors, a transgenic zebrafish constitutively expressing the krasV12 oncogene in the liver was previously generated by our laboratory. Although this model depicted and uncovered the conservation between zebrafish and human liver tumorigenesis, the low tumor incidence and early mortality limit its use for further studies of tumor progression and inhibition. Here, we employed a mifepristone-inducible transgenic system to achieve inducible krasV12 expression in the liver. The system consisted of two transgenic lines: the liver-driver line had a liver-specific fabp10 promoter to produce the LexPR chimeric transactivator, and the Ras-effector line contained a LexA-binding site to control EGFP-krasV12 expression. In double-transgenic zebrafish (driver-effector) embryos and adults, we demonstrated mifepristone-inducible EGFP-krasV12 expression in the liver. Robust and homogeneous liver tumors developed in 100% ...
View Notes - Week One from ANTH 2020 at Colorado. of their lives Fight Against Death Donor Transplants Transgenic Pigs • (hyper)Acute Immune Response Fetal Tissues • Blastocyst • Totipotent
TT-RIIP International Course, TRANSGENIC TECHNOLOGIES in MODELING HUMAN DISEASES: Principles, Associated Technologies, Animal Management and Ethics, 5-13 June 2017, Athens, ...
Alex Palazzo has a little post on the "brainbow mouse", created using some of the transgenic methods mentioned by amenestic in a post a while back. Each individual neuron in a given mouse brain expresses a random combination of fluorescent proteins, allowing analysis with the naked eye. Pretty amazing stuff ...
P-glycoproteins can cause multidrug resistance in mammalian tumor cells by active extrusion of cytotoxic drugs. The natural function of these evolutionarily conserved, membrane-bound ATP binding transport proteins is unknown. In mammals, P-glycoproteins are abundantly present in organs associated with the digestive tract. We have studied the tissue-specific expression of Caenorhabditis elegans P-glycoprotein genes pgp-1 and pgp-3 by transformation of nematodes with pgp-lacZ gene fusion constructs in which the promoter area of the pgp genes was fused to the coding region of lacZ. Expression of pgp-1 and pgp-3, as inferred from pgp-lacZ transgenic nematodes, was confined to the intestinal cells. The expression patterns of both genes were virtually indistinguishable. Quantitative analysis of pgp mRNA levels during development showed that pgp-1, -2, and -3 were expressed throughout the life cycle of C.elegans, albeit with some variation indicating developmental regulation. The expression of P-glycoprotein
Cell cycle analysis of transgenic zebrafish embryos expressing PCNA-CB. (A) Overview of the dorsal midbrain of a wnt1:gal4,UAS:GFP (green); UAS:PCNA-CB (magenta
BioAssay record AID 620365 submitted by ChEMBL: Antiangiogenic activity in fli-1:enhanced GFP expressing transgenic zebrafish embryo assessed as inhibition of neovacularisation at 5 uM after 24 hrs relative to control.
The study is the first to document the rise of mutations that make mosquitoes resistant to a gene drive, due to natural selection. These findings will allow researchers to make better predictions of how a gene drive will proceed and to improve the design of future gene drives to decrease the likelihood of resistance.. Tony Nolan adds: Reducing the numbers of mosquito vectors has been the most effective tool to date for the control of malaria, so self-sustaining gene drives designed with this purpose have great potential. However gene drives are not a silver bullet and just like antibiotics can select for resistance in bacteria, gene drives can be susceptible to resistance at their target site. The novelty of this study is not that resistance emerges - we have been planning strategies to deal with this from the start - but that it documents the way it emerges and the way it is selected over generations. This work will help a lot in planning for and managing the emergence of ...
In August, the first cloned pig with Alzheimers disease will be born in Denmark.. Responsible for this breakthrough are scientists from the universities of Copenhagen and Århus, Denmark in their effort towards finding a cure for Alzheimers disease.. The said pigs have been genetically modified to function as animal models for Alzheimers disease - a brain disorder suffered by an approximately 24 million people globally.. According to Ingrid Brück Bøgh from the Department of Large Animal Sciences, University of Copenhagen:. "In the light of the intense focus on medical research at the University of Copenhagen and the continuous expansion of the pharmaceutical industry in Denmark, the ability to produce transgenic pig models for human diseases is a major prerequisite for future progress in this area.. The upcoming birth of these transgenic pig models constitutes a fantastic success for us. It is also a demonstration of the excellent cross-disciplinary collaboration between the experts at both ...
One of the main concerns over gene drive is its potential long‐term effects. The designated effects on the targeted populations will be fast-within a few years-while long‐term effects on ecosystems may take decades to appear and are extremely unpredictable. The time frame of gene drive perfectly fits the economic development strategies dominant today in agribusiness, with a focus on short‐term return on investments and disdain for long‐term issues. The current economical system based on productivity, yields, monoculture, and extractivism [7] is a perfect match for the operating mode of gene drive. In addition, agri‐food industry decision centers are rarely located near the production sites. They will be inclined to disregard the ecological long‐term risks as they only concern local human populations in their exploited lands. Gene drive then becomes an issue of environmental justice.. The scarce use of gene drive, if concerted, cautious and controlled, may not cause any ecological ...
One of the main concerns over gene drive is its potential long‐term effects. The designated effects on the targeted populations will be fast-within a few years-while long‐term effects on ecosystems may take decades to appear and are extremely unpredictable. The time frame of gene drive perfectly fits the economic development strategies dominant today in agribusiness, with a focus on short‐term return on investments and disdain for long‐term issues. The current economical system based on productivity, yields, monoculture, and extractivism [7] is a perfect match for the operating mode of gene drive. In addition, agri‐food industry decision centers are rarely located near the production sites. They will be inclined to disregard the ecological long‐term risks as they only concern local human populations in their exploited lands. Gene drive then becomes an issue of environmental justice.. The scarce use of gene drive, if concerted, cautious and controlled, may not cause any ecological ...
During vertebrate embryogenesis, the cranial neural crest (CNC) forms at the neural plate border and subsequently migrates and differentiates into many types of cells. The transcription factor Snai2, which is induced by canonical Wnt signaling to be expressed in the early CNC, is pivotal for CNC induction and migration in Xenopus. However, snai2 expression is silenced during CNC migration, and its roles at later developmental stages remain unclear. We generated a transgenic X. tropicalis line that expresses enhanced green fluorescent protein (eGFP) driven by the snai2 promoter/enhancer, and observed eGFP expression not only in the pre-migratory and migrating CNC, but also the differentiating CNC. This transgenic line can be used directly to detect deficiencies in CNC development at various stages, including subtle perturbation of CNC differentiation. In situ hybridization and immunohistochemistry confirm that Snai2 is re-expressed in the differentiating CNC. Using a separate transgenic Wnt reporter line
Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. The linker protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH
Behrendorff, N, Behrendorff, J, Wall, A, Scott, E and Thorn, P (2011). A Novel Transgenic Zebrafish Model for Studying Secretion in the Exocrine Pancreas. In: Abstracts of Papers Submitted to the 42nd Annual Meeting of the American Pancreatic Association. 42nd Annual Meeting of the American Pancreatic Association, Chicago, IL, United States, (1314-1314). 2-5 November 2011. doi:10.1097/MPA.0b013e318232ea83 ...
He has led the movement to shine the spotlight," says Marc Lipsitch, an epidemiologist at Harvard University involved in biosafety issues. "Its not that common to be at the beginning of your career and already be thinking of the moral, ethical, and policy implications.". A gene drive is a genetic addition made to a mosquito or other organism that is able to spread through a population of animals in the wild and potentially act as a doomsday gadget, driving it out of existence. The technology presents challenges not only because it could extinguish a species but because by its very nature it can spread widely, including as the result of a lab accident.. "This is the perfect example of a technology that needs to be community-guided from the beginning," says Esvelt. "Its meaningless to talk about engaging the public in science if science is still going to develop the product and then say, What do you think?". Esvelt says hes started a new project, called Responsive Science, along with MIT ...
Gene drive systems distort the rule that there is a 50:50 chance of a gene copy being passed on. This promotes the inheritance of a particular copy of a gene from the parent to offspring. When coupled to a genetic trait that affects an individuals survival or ability to reproduce, it becomes a powerful tool that can be used for population control or even local elimination.
In lab populations of genetically engineered mosquitoes, mutations arose that blocked the gene drive’s spread and restored female fertility.
Read chapter 3 Case Studies to Examine Questions About Gene-Drive Modified Organisms: Research on gene drive systems is rapidly advancing. Many proposed a...
Public fears and concerns towards transgenic plant or animal have been there for years even though the scientific expects in China, at least, acclaimed that they are safe. The reason why people are afraid of transgenic technology and furthermore reject it is that public people dont know it at all, or have limited understanding.. You must have read lots of articles explaining why transgenic technology is safe, or on the other hand, dangerous. And here I believe current products of transgenic technology in your daily life are safe and healthy, because most of them are protein product indeed. It is the exogenous genes are translocated and expressed in the host, but the outcome is protein according to the known central dogma, hence the protein cannot hybridize with your genome so that you will not be mutated to Rice-Man. No need to panic.. ...
Transgenic mosquitoes that could eradicate malaria. Unfortunately, it is potentially the most hazardous genetically modified organism (GMO) to have be
Gene drive is a mechanism that can promote the preferential inheritance of a beneficial genetic trait, thereby increasing its prevalence in a population. A variety of gene drive mechanisms occur in nature that can cause specific genetic elements to spread throughout populations in varying degrees. Researchers have long sought to harness these naturally occurring gene drive mechanisms to prevent the transmission of mosquito or other insect-borne diseases that pose some of societys most intractable public health problems.. ...
Energy homeostasis is accomplished through a highly integrated and redundant neurohumoral system. Recently, novel molecular mediators and regulatory pathways for feeding and body weight regulation have been identified in the brain and the periphery. Because of the multitude and complexity of disturbances in energy intake, expenditure, and partitioning that are associated with obesity, it has been difficult to determine which abnormalities are causative versus less important phenomena that are consequences of the altered neuroendocrine and metabolic milieu. Transgenic technology has provided new opportunities to modify the complex body weight-regulating system and to assess the relative importance of the individual components. Observations of mutant mice have shed new light on the understanding of energy homeostasis equation. Once created, transgenic animal models may be useful in assessing the efficacy or determining the mode of action of potential new therapeutic agents. However, the ...
Advances in single-cell technologies have revealed vast differences between cells once thought to be in the same category, calling into question how we define cell type in the first place ...
Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies. ...
091011 - Animais Transg nicos: Conceito, Metodologias e Aplica es - Transgenic animals: concept, methodologies and applications | Veterinaria.org . La primera comunidad veterinaria de habla hispana con presencia en Espa a y Am rica del Sur.
The simpler procedure, which uses a single tagged secondary antibody, can often be used (8). Animals are best perfusion fixed with PAF (9 see Chapter 45). The
TY - JOUR. T1 - Analysis of the N-glycans of recombinant human Factor IX purified from transgenic pig milk. AU - Gil, Geun Cheol. AU - Velander, William H.. AU - Van Cott, Kevin E.. PY - 2008/7/1. Y1 - 2008/7/1. N2 - Glycosylation of recombinant proteins is of particular importance because it can play significant roles in the clinical properties of the glycoprotein. In this work, the N-glycan structures of recombinant human Factor IX (tg-FIX) produced in the transgenic pig mammary gland were determined. The majority of the N-glycans of transgenic pig-derived Factor IX (tg-FIX) are complex, bi-antennary with one or two terminal N -acetylneuraminic acid (Neu5Ac) moieties. We also found that the N-glycan structures of tg-FIX produced in the porcine mammary epithelial cells differed with respect to N-glycans from glycoproteins produced in other porcine tissues. tg-FIX contains no detectable Neu5Gc, the sialic acid commonly found in porcine glycoproteins produced in other tissues. Additionally, we ...
CRISPR gene drive has recently been proposed as a promising technology for population management, including in conservation genetics. The technique would consist in releasing genetically engineered individuals that are designed to rapidly propagate a desired mutation or transgene into wild populations. Potential applications in conservation biology include the control of invasive pest populations that threaten biodiversity (eradication and suppression drives), or the introduction of beneficial mutations in endangered populations (rescue drives). The propagation of a gene drive is affected by different factors that depend on the drive construct (e.g. its fitness effect and timing of expression) or on the target species (e.g. its mating system and population structure). We review potential applications of the different types of gene drives for conservation. We examine the challenges posed by the evolution of resistance to gene drives and review the various molecular and environmental risks associated with
TY - JOUR. T1 - Expression of cytochrome P45011B1 mRNA in the brain of normal and hypertensive transgenic rats. AU - Erdmann, Bettina. AU - Gerst, Hellmut. AU - Lippoldt, Andrea. AU - Buelow, Hannes E.. AU - Ganten, Detlev. AU - Fuxe, Kjell. AU - Bernhardt, Rita. PY - 1996/9/9. Y1 - 1996/9/9. N2 - Cytochrome P45011B1 (11β-hydroxylase) was detected in the brain of male rats by in situ hybridization methods. Normal Sprague-Dawley rats were compared to the transgenic strain TGR(mRen2)27, characterized by the expression of the murine Ren-2(d) renin gene and the development of severe hypertension. Specific riboprobes were generated by in vitro transcription of a 152 base-pair long cDNA template. 35S-labeled riboprobes were hybridized to cryostat sections from adrenal glands and from two different levels of the brain using standard protocols and varying washing conditions. After exposure of the radiolabeled sections to X-ray film, the signals were quantified and compared. Following autoradiography ...
J. Pathol. 163:2155-2164. , 2001, Amyloid p protein forms ion channels: implications for Alzheimers disease pathophysiology. FASEB J. 15: 2433-2444. -C, Hall, D. , Mathis, C. , 2001, Visualization of fibrillar amyloid deposits in living, transgenic Caenorhabditis elegans animals using the sensitive amyloid dye, X-34. Neurobiol Aging 22:217-226. , 2004, Single chain variable fragments against B-amyloid (AB) can The Contribution of Microscopy to the Study of Alzheimers Disease 39 inhibit AB aggregation and prevent AB-induced neurotoxicity. Interestingly, a rapidly-formed but transient nanocrystalhne from of a 14-amino acid Ap peptide has been described by Otzen and Oliveberg (2004). Using TEM these workers showed that the nanocrystalline form of this peptide leads to the formation of a tangled aggregate (hours) and amyloid fibres (days). 2 Ap protofilaments Definition of the P-sheet-containing protofilament that can be formed by Ap and several other fibril-forming amyloidogenic peptides is by no ...
Our lab studies the alternative splicing of pre-mRNAs. In Drosophila, alternative splicing plays a central role in sex determination. We have been using the sex-determination system to study factors that influence alternative splicing and to determine the mechanisms by which they do so. Several of the proteins we are studying belong to the serine/arginine-rich (SR) family of splicing factors. These proteins usually bind to sequences located within exons, known as exonic splicing enhancers (ESEs) and activate nearby splice sites. We have found that an SR factors can repress splicing when bound within an intron. Using in vitro splicing assays and Drosophila genetics we are determining how splicing activation and repression differ. A second interest of the lab is in genetic models for muscular dystrophy. Recently we have developed a transgenic Drosophila model for facioscapulohumeral muscular dystrophy (FSHD) a poorly understood late-onset disease that affects specific muscle groups in humans. We ...
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This study has demonstrated that microparticle bombardment is a simple and efficient technique for generating stable transgenic lines in C. elegans. We have found that a substantial proportion of the transgenic lines generated by microparticle bombardment contain a low number of copies of the transforming DNA integrated into a chromosome, resulting in stable transmission of the transgenic DNA over many generations. A critical factor in the success of this microparticle bombardment transformation strategy is the use of a selectable cotransformation marker to identify rare transformed animals within the population of bombarded animals and their descendants. For the experiments described in this article, we bombarded unc-119 mutants with plasmids containing an unc-119 rescuing fragment and were able to identify transformed animals based on their ability to survive starvation and on their non-Unc phenotype.. In some cases, the unc-119 gene may be an unsuitable cotransformation marker due to ...
Regulating transgenic technology in China: Law, regulation, and public policy. Yinliang Liu Dr. of Laws, M.S. (Biology), Associate Professor Vice Director, Institute of IP Law Director, Bio-Law Research Center China University of Political Science and Law 3 December 2007. Outline. Slideshow 449280 by tirza
Confocal micrograph of the brain of a transgenic zebrafish embryo. Some neurons express the green fluorescent protein (GFP) - shown in green under the...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Not everyone is convinced that this optimistic view is warranted. "Its a false security," said Ethan Bier, a geneticist at the University of California, San Diego. He said that while such a strategy is important to study, he worries that researchers will be fooled into thinking that forms of resistance offer "more of a buffer and safety net than they do.". And while mathematical models are helpful, researchers stress that models cant replace actual experimentation. Ecological systems are just too complicated. "We have no experience engineering systems that are going to evolve outside of our control. We have never done that before," Esvelt said. "So thats why a lot of these modeling studies are important-they can give us a handle on what might happen. But Im also hesitant to rely on modeling and trying to predict in advance when systems are so complicated.". Messer hopes to put his theoretical work into a real-world setting, at least in the lab. He is currently directing a gene drive ...
Penn State and Agariger, Inc. have patented the technology of making new transgenic mushrooms, which have increased hope of using mushrooms for the mass
Transgenic mice and methods of preparing such mice are disclosed. The mice exhibit decreased platelet counts and/or megakaryocyte leukemia.
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LONDON (Reuters) - Rodents have joined mosquitoes in the cross-hairs of scientists working on a next-generation genetic technology known as "gene drive" to control pests.. Researchers in Scotland said on Tuesday they had developed two different ways to disrupt female fertility in rats and mice, building on a similar approach that has already been tested in the lab to eliminate malaria-carrying mosquitoes.. So-called gene drives push engineered genes through multiple generations by over-riding normal biological processes, so that all offspring carry two copies. Usually, animals would receive one copy of a gene from the mother and one from the father.. The technique is extremely powerful but also controversial, since such genetically engineered organisms could have an irreversible impact on the ecosystem.. Concerns about the proliferation of mutant species have led some to call for a gene drive ban, but Bruce Whitelaw of the University of Edinburghs Roslin Institute believes that would be short ...
TRANSGENIC RABBIT MODELS FOR THE STUDY OF ATHEROSCLEROSIS John M. Taylor and Jianglin Fan Gladstone Institute of Cardiovascular Disease, the Department of Physiology, and the Cardiovascular Research Institute, University of California, San Francisco, CA TABLE OF CONTENTS ...
Naturally occurring mutations involving the nervous system have provided virtually all of our current understanding of the genetic regulation of neural development (Caviness and Rakic, 1978). The difficulty of isolating the corresponding genes, however, has precluded a molecular analysis of these mutants. Insertional mutagenesis, induced by microinjection of DNA into fertilized ova to produce transgenic animals, provides a molecular tag that marks the site of the mutational event. In this article, we describe a transgenic neurological mutation, designated wocko (Wo), which disrupts the development of the inner ear. These mutant mice display a dominant behavioral phenotype that consists of circling, hyperactivity, and head tossing, reminiscent of the shaker/waltzer class of mutants, and they display a recessive homozygous sublethal phenotype. Anatomical analyses showed that both structural and neural components of the vestibular system were disrupted, while analyses of mutant fetuses showed that ...
This laboratory manual, published in cooperation with the International Society for Transgenic Technology (ISTT), provides almost all current methods that can be applied to the creation and analysis o
A postdoctoral position is available at the University of California, San Francisco, to analyze transgenic zebrafish that model neurodegenerative diseases. Required skills include: histology and immunohistochemistry, familiarity with brain anatomy, and molecular biology. Prior experience with zebrafish is desirable but not essential. Please email CV and three letters of reference to: Su Guo suguo at itsa.ucsf.edu ...
Background. Transgenic animal technology includes the process of inserting functional foreign genes into animals and using them as a tool to research intricate biological processes. Transgenic Animals are animals that have DNA introduced into their cells artificially. These animals become important instruments in exploring regulation of various genetic pathways, gene expression* and cellular processes. By inserting a gene into a live organism, scientists can explore the function of this gene in various environments. Transgenic animals serve a variety of different functions, proving them to be powerful research tools.Transgenic animals can serve as distinctive models for disease, and are made specifically to answer precise biological questions. ...
Engineered synthetic species-like barriers were recently described by Maselko et al (2017) in Nature Communications and the work has interesting implications for genetic control strategies and gene drive containment. There is an ever-increasing interest in manipulating natural populations using genetic […]. Read More ». ...
Transgenic rats with components of the human RAS provide an opportunity for the study of the human RAS and human renin inhibitors in a rodent model readily suitable for physiological experimentation. We used transgenic rats with a high overexpression of human angiotensinogen19 to study the formation of angiotensin peptides at the level of the vascular wall. Our data show that human angiotensinogen is present at the vascular wall in these rats. Furthermore, human renin can be taken up from the circulation and remains active much longer than its presence in the circulation would explain. Even after its disappearance from the circulation, the enzyme continued to cleave human angiotensinogen locally in the tissues, resulting in the release of Ang I and II. The enzymatic activity of human renin was promptly inhibited by a specific human renin inhibitor.. The species specificity of the renin-angiotensinogen interaction does not allow the study of human angiotensinogen or renin in rats.19 Specific ...
BACKGROUND: Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. RESULTS: To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C | T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre
Macquarie University researchers have developed the first zebrafish model of the neurodegenerative Machado-Joseph Disease - and have used this model to test drugs that could potentially be used to treat the disease, which disproportionately affects Indigenous Australians.. Machado-Joseph Disease, or spinocerebellar ataxia-3, is a hereditary disease caused by a gene mutation, which leads to a progressive loss of muscle control and movement. Most people living with MJD are wheelchair bound and need constant support within 15 years of symptoms first emerging.. Researchers gave the zebrafish the human disease-causing gene, creating the first transgenic zebrafish model of MJD, allowing them to compare the movement, pathology and lifespan of fish carrying the healthy version of the human gene to those with the disease-causing version.. "Zebrafish are small and transparent, allowing us to see how a disease develops. Being able to use zebrafish to model MJD is a great win for those of us working to ...
The dopamine transporter (DAT) plays a pivotal role in maintaining optimal dopamine signaling. DAT-overactivity has been linked to various neuropsychiatric disorders yet so far the direct pathological consequences of it has not been fully assessed. We here generated a transgenic rat model that via pronuclear microinjection overexpresses the DAT gene. Our results demonstrate that DAT-overexpression induces multiple neurobiological effects that exceeded the expected alterations in the corticostriatal dopamine system. Furthermore, transgenic rats specifically exhibited behavioral and pharmaco-therapeutic profiles phenotypic of repetitive disorders. Together our findings suggest that the DAT rat model will constitute a valuable tool for further investigations into the pathological influence of DAT overexpression on neural systems relevant to neuropsychiatric disorders.. ...
Suppression of dengue and malaria through releases of genetically engineered mosquitoes might soon become feasible. Aedes aegypti mosquitoes carrying a conditionally lethal transgene have recently been used to suppress local vector populations in small-scale field releases. Prior to releases of transgenic insects on a wider scale, however, most regulatory authorities will require additional evidence that suppression will be effective in natural heterogeneous habitats. We use a spatially explicit stochastic model of an Ae. aegypti population in Iquitos, Peru, along with an uncertainty analysis of its predictions, to quantitatively assess the outcome of varied operational approaches for releases of transgenic strains with conditional death of females. We show that population elimination might be an unrealistic objective in heterogeneous populations. We demonstrate that substantial suppression can nonetheless be achieved if releases are deployed in a uniform spatial pattern using strains combining multiple
Animal models have been used to examine the development of the classic phenotypic findings of LVH, myocyte disarray and interstitial fibrosis. In a transgenic rabbit model of HCM (β-MyHC-Q403), myocyte disarray occurred before cellular hypertrophy and fibrosis (10). The transgenic rabbit model is interesting because beta-myosin heavy chain is the predominant protein, as in humans; this is unlike in mice, in which alpha-myosin heavy chain is the predominant protein. With respect to imaging findings, a reduction in septal and lateral systolic and diastolic mitral annulus velocities was the earliest observation when transgenic mutant animals were compared with nontransgenic or wild-type animals (11). Interestingly, myocardial velocities were not related to disarray, hypertrophy, or collagen volume fraction. Conversely, reduced calcium sensitivity of myofibrillar ATPase activity was detected in these animals at the same time abnormal myocardial function was observed by imaging. With disease ...
My lab uses zebrafish as a model to study myelination in the development central nervous system. The small size, optical transparency, relative simplicity, and rapid development of zebrafish embryos are properties that allow direct observation of entire developmental (or repair) events as they occur in live animals. We have developed a non-invasive transgenic method to induce demyelination in zebrafish and have also generated a suite of tools to visualise myelin and myelinated axons at high-resolution in live zebrafish, which allows us to observe cellular, sub-cellular and molecular behaviours during myelination, demyelination, and remyelination as they occur in a living animal. Zebrafish are well established as a powerful system with which to identify new genes required for biological events. In a genetic screen carried out at Stanford University I identified new roles for genes with known involvement in myelination, established zebrafish models of human disease, and identified new genes ...
The Megason lab is interested in how the program contained in the genome is executed during development to turn an egg into an embryo. We use confocal/2-photon imaging of living, transgenic zebrafish embryos to watch biological circuits function in vivo and use these data in cell-based, quantitative modeling.
MicroRNAs are a well-studied class of non-coding RNA and are known to regulate developmental processes in eukaryotes. Their role in key biological processes such as vasculature development has attracted interest. However, a comprehensive understanding of molecular regulation of angiogenesis and vascular integrity during development remains less explored. Here we identified miRNAs involved in the development and maintenance of vasculature in zebrafish embryos using a reverse genetics approach. Using a combination of bioinformatics predictions and literature based evidences we mined over 701 Human and 329 Zebrafish miRNAs to derive a list of 29 miRNAs targeting vascular specific genes in zebrafish. We shortlisted eight miRNAs and investigated their potential role in regulating vascular development in zebrafish transgenic model. In this screen we identified three miRNAs, namely miR-1, miR-144 and miR-142a-3p that have the potential to influence vascular development in zebrafish. We show that miR-142a-3p
Abstract. To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA) gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox)-regulated gene expression in transgenic rats. In the two transmittable lines, tTA-mediated activation of the reporter gene was fully subject to regulation by Dox. Dox dose-dependently suppressed tTA-activated gene expression. The washout time for the effects of Dox was dose-dependent. We tested a complex regime of Dox administration to determine the optimal effectiveness and washout duration. Dox was administered at a high dose (500 μg/ml in drinking water) for two days to reach the effective concentration, and ...
Introduction. Abbreviations and Acronyms. 1. FROM THE GENE TO THE TRANSGENIC ANIMAL.. Genome composition.. Gene structure.. The number of genes in genomes.. The major techniques of genetic engineering.. The systematic description of genomes.. Classical genetic selection.. Experimental mutation in genomes.. 2. TECHNIQUES FOR CLONING AND TRANSGENESIS.. Cloning.. Gene therapy.. Techniques of animal transgenesis.. 3. APPLICATIONS OF CLONING AND TRANSGENESIS.. Applications of animal cloning.. Applications of animal transgenesis.. 4. LIMITS AND RISKS OF CLONING, GENE THERAPY AND TRANSGENESIS.. Limits and risks of cloning.. Limits and risks of gene therapy.. Limits and risks of transgenesis.. Conclusion and Perspectives.. References.. Index. ...
THE zebrafish (Danio rerio) is a powerful tool for understanding vertebrate biology. The usefulness of this model organism is bolstered by the availability of a "finished" sequenced and annotated genome (Howe et al. 2013; Flicek et al. 2014). As a natural extension of this resource, there are several high-throughput efforts to systematically mutagenize all zebrafish protein-coding genes (Moens et al. 2008; Kettleborough et al. 2013; Varshney et al. 2013a,b).. In addition to such projects, the combination of a sequenced genome and developments in targeted nuclease technology mean that the zebrafish community is now able to rapidly take advantage of custom genome-editing technologies (Doyon et al. 2008; Bedell et al. 2012; Hruscha et al. 2013; Hwang et al. 2013; Jao et al. 2013). CRISPRs in particular provide an efficient, easy, and inexpensive means of manipulating and interrogating the genome (Jinek et al. 2012; Cong et al. 2013; Mali et al. 2013). However, because there are very few hardy ...
Gene drive systems are sensitive to the evolution of resistance in the form of polymorphisms in the guide RNAs target DNA sequence. Champer et al. (2017) have recently reported on their exploration of how Cas9 expression patterns as well as different genetic backgrounds impact the evolution of resistance to a gene drive system in Drosophila melanogaster.. Homing-based gene drive systems depend upon a high rate of Homology-Directed-DNA-Repair (HDR) following target site cleavage. When and where Cas9 cleavage occurs can impact the proportion of repair events that result from Non Homologous End Joining (NHEJ) and HDR. For example, if cleavage and repair occur in gametes then one would expect NHEJ-based repair to occur since there would be no homologous chromosome upon which HDR would depend.. Champer et al. created two Cas9-based drive systems; one in which Cas9 expression was regulated by the promoter from vasa and the other in which Cas9 expression was regulated by the promoter from nanos. Both ...
Oxford Global are proud to present the 2nd Genome Editing USA Congress, 2nd Annual Advances in Transgenic Congress USA and Synthetic Biology USA Congress taking place on 10-11 May 2018, Boston USA
Crossing of transposase and transposon transgenic mice yields experimental mice in which the transposon is mobilizing in the soma due to the presence of both transposase and transposons. Singly transgenic littermates serve as controls. Crossing T2/Onc2 transgenics to Rosa26SB11 transgenics resulted in 5.6% to 12.5% doubly transgenic offspring depending on the T2/Onc2 concatomer used. The observed sub-Mendelian ratio of genotypes was due to high rates of embryonic lethality in double transgenics. All T2/Onc2;Rosa26SB11 mice that survived to birth were moribund by 114 days of age. Twenty-three of 24 mice developed hematopoietic malignancies (mainly T-cell lymphoma) and 2 mice developed medulloblastomas. In addition to frank neoplasia, 4 mice also had hyperplasia of the intestine or pituitary gland ( 15). These results contrast to experiments using the lower-copy T2/Onc concatomers and CAGGS-SB10 transposase in which doubly transgenic mice had life spans comparable with controls. Although somatic ...
Study obesity, lipodystrophy, polyglucosan disorders, type 1 diabetes, type 2 diabetes, bone-mineral metabolic disorders or muscle glycogen disorders, etc.
Mouse models for hepatitis, nephritis, bowel disease, such as systemic lupus erythematosus, arthritis, allergy, hepatitis, leishmaniasis or chlamydial infection.
In general, gene expression (in terms of mRNA production) should be proportional to the number of copies of the gene present in the genome. If multiple alleles of a gene are present, the expression of each should be similar. So for a gene with 2 alleles (call them A and a), the level of expression in an animal homozygous for A would be 2(A) (since it has 2 copies of the allele, assuming it got one from the father and one from the mother). A heterozygote would show levels of expression of 1(A) + 1(a), and a homozygote for a would be 2(a). This should hold true for genes introduced by transgenic methods as well, assuming that your transgene is present in similar numbers as the complementary endogenous gene, and that it did not insert into a genomic location that somehow inhibits it from being expressed. Keep in mind that this is a rather idealized explanation and there are a number of things that are not taken into account. If, for example, the function of the product of gene A is to stimulate ...
Officials from the FBI to the United Nations bioweapons office are concerned enough about gene drives that they are scrambling to get ahead of them.
Home page banner reprinted from Hearing Research, 341, Monroe, J.D. et al., Hearing sensitivity differs between zebrafish lines used in auditory research, 220-231, Copyright (2016) with permission from Elsevier ...
The health relevance of Drosophila as a model system extends beyond conserved human genes. This report describes testing compounds in mosquito, Drosophila and human cells in an effort to identify compounds that kill mosquitoes without affecting related insects like fruit flies, or humans ...
Systems Pharmacology and Translational Therapeutics involves the discovery of new drugs, the investigation of how drugs work and the use of drugs to probe mechanisms of disease that spans the most fundamental aspects of basic research, through transgenic animal models, to clinical investigation.
We have used somatic brain transgenic technology to deliver the BRI2 and BRI2-Aβ1-40 transgenes to the brains of APP mouse models. The studies with BRI2-Aβ1-40 confirmed previous studies obtained using conventional transgenic mice expressing BRI2-Aβ1-40 (McGowan et al., 2005; Kim et al., 2007). Thus, the somatic brain transgenic BRI2-Aβ1-40 studies provide additional validation for this rapid cost-effective method of manipulating gene expression in the brain (Levites et al., 2006b).. The novel result from these studies was the finding that BRI2 suppresses Aβ deposition in APP CRND8 transgenic mice to an extent equivalent to Aβ1-40. Although it is not possible to completely rule out subtle effects on Aβ generation that could influence deposition, we found no evidence that the suppressive effect was mediated by alterations in APP processing or Aβ production. Instead, we find that the suppressive effect of BRI2 is likely to be mediated by inhibition of Aβ aggregation by the secreted ...
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Hi, I want to seperate leukocytes from whole blood and do cytospins. I am having problems with cells lysing. I was wondering if anybody knows the osmolarity of zebrafish blood and if there is a recommended PBS, HBSS... for blood cells of zebrafish. Any ideas? Thanks ...
MyElimu is a website that brings together students from all over Tanzania as they discuss various subjects and academic matters from O Level to A Level.
Are Carbs Really the Culprit . . . Is Cutting Them The Answer? Would you like to lose weight quickly? Do you presently consume breads, pastas, and an occasional donut? OK, just stop. You will lose weight. When the scale is used as a gauge, cutting carbs may be the most effective way to drop…
مقاله ISI انگلیسی شماره 78876 - ترجمه نشده - موضوع : الگوریتم های تکاملی - 10 صفحه - سال انتشار : 2014 - منبع : الزویر ساینس دایرکت
Humanised fruit fly models are transgenic Drosophila melanogaster strains expressing human genes. Specifically, we study the characteristics of fly models expressing human genes involved in neurological disorders such as Alzheimers and Parkinsons Diseases (AD and PD). Interestingly, these Drosophila neurodegenerative disease models show a high degree of conservation in the fundamental biological pathways and in the molecular, genetic and pathophysiological aspects of neurodegenerative human diseases. These characteristics explain why Drosophila models have paved the way for the development of initial fast screening for potential drug candidates in vivo, and represent also a promising tool for biomedical research in neuroscience ...
Purpose : The purpose of the current study is to determine in-depth functions of selected transcripts that are enriched in rod photoreceptors, in order to gain insights into intrinsic mechanisms underlying rod development and regeneration. Methods : We used a transgenic zebrafish line (XOPS:eGFP) in which rod photoreceptors express green fluorescent protein (GFP) as a model organism for this study. RNA-seq of FACS-sorted dissociated retinal cells was performed to identify differentially expressed (in GFP+ vs. GFP- cells) transcripts with FDR , 0.01. Selected rod-specific genes were prioritized for further qRT-PCR and in situ hybridization studies at different life stages of the zebrafish, and for qRT-PCR studies of rods that regenerated after widespread chemical lesioning of the retina. The rxrγa gene was of particular interest as its transcript was enriched in rods, while previous studies in mouse indicated roles in cone determination. Therefore, a new rxrγa mutant line was created by ...
Purpose: Emran et al (2010) reported that the amplitudes of the electroretinograms (ERGs) recorded from isolated eyes of larval zebrafish were normal throughout the day, but were almost absent after several hours of darkness at night. The purpose of our study was to confirm this circadian rhythm of the ERGs in living zebrafish.. Methods: Initially, zebrafish (Danio rerio) were kept in a 14:10 light:dark cycle (room fluorescent light, 9:00 to 23 hours). ERGs were elicited by stimulus intensities of 790 mW/m2 and durations of 1000 msec. The ERGs were recorded with an Ag/AgCl wire electrode that was inserted into a glass micropipette filled with E3 medium. A glasspipette electrode was positioned in the center of the cornea and a reference electrode was an Ag/AgCl pellet that placed beneath the larvae body. The zebrafish was anesthetized by 3-aminobenzoic acid methylester and placed on its side on a moisture sponge with one eye facing toward a light. We recorded ERGs of larval (5 days ...
Massachusetts General Hospital Background: Cleft lip and/or palate (CL/P) is the most frequent craniofacial birth defect. Transcription factor IRF6 has been confirmed as a key locus for syndromic and non-syndromic CL/P. In order to understand irf6 function during palate development and its role in cleft malformation, we are generating transgenic irf6 reporter line for use in mechanistic analysis.. Methods: A 7.185 kb zebrafish irf6 promoter sequence was amplified from the irf6 bacterial artificial chromosome. The Tg:irf6:eGFP transgenic animal was generated using Gateway system, with Tol2 transposase mediating germline integration. Progeny of stable transgenic lines were analyzed by compound and confocal microscopy.. Results: Expression of irf6 was detected at single cell stage, confirming the presence of irf6 as a maternal transcript (Figure. 1). Irf6 expression continued throughout gastrulation, then localized in the otic placode and migrating cranial neural crest cells. Later in ...
TY - JOUR. T1 - Inhibition of TBK1/IKKε Promotes Regeneration of Pancreatic β-cells. AU - Xu, Jin. AU - Jia, Yun Fang. AU - Tapadar, Subhasish. AU - Weaver, Jessica D.. AU - Raji, Idris O.. AU - Pithadia, Deeti J.. AU - Javeed, Naureen. AU - García, Andrés J.. AU - Choi, Doo Sup. AU - Matveyenko, Aleksey V. AU - Oyelere, Adegboyega K.. AU - Shin, Chong Hyun. PY - 2018/12/1. Y1 - 2018/12/1. N2 - β-cell proliferation induction is a promising therapeutic strategy to restore β-cell mass. By screening small molecules in a transgenic zebrafish model of type 1 diabetes, we identified inhibitors of non-canonical IκB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε), as enhancers of β-cell regeneration. The most potent β-cell regeneration enhancer was a cinnamic acid derivative (E)-3-(3-phenylbenzo[c]isoxazol-5-yl)acrylic acid (PIAA), which, acting through the cAMP-dependent protein kinase A (PKA), stimulated β-cell-specific proliferation by increasing cyclic AMP (cAMP) ...
Lorraine Lacovitti, Xiaotao Wei, Jingli Cai, Eric W. Kostuk, Ruihe Lin, Alexander Gorodinsky, Philip Roman, Gretchen Kusek, Sonal S. Das, Audrey Dufour, Terina N. Martinez, and Kuldip D. Dave. Parkinson disease (PD) is the second leading neurodegenerative disease in the US. As there is no known cause or cure for PD, researchers continue to investigate disease mechanisms and potential new therapies in cell culture and in animal models of PD. In PD, one of the most profoundly affected neuronal populations is the tyrosine hydroxylase (TH)-expressing dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). These DA-producing neurons undergo degeneration while neighboring DA-producing cells of the ventral tegmental area (VTA) are largely spared. To aid in these studies, The Michael J. Fox Foundation (MJFF) partnered with Thomas Jefferson University and Taconic Inc. to generate new transgenic rat lines carrying the human TH gene promoter driving EGFP using a 11 kb construct used ...
Transgenic rats have been used as model animals for human diseases and organ transplantation and as animal bioreactors for protein production. In general, transgenic rats are produced by pronuclear microinjection of exogenous DNA. Improvement of post-injection survival has been achieved by micro-vibration of the injection pipette. The promoter region, structural gene, chain length and strand ends of the exogenous DNA are not involved in the production efficiency of transgenic rats. Exogenous DNA prepared at 5 μg/ml seemed to be better integrated than lower and higher concentrations. Intracytoplasmic sperm injection (ICSI) has been successfully achieved in rats using a piezo-driven injection pipette. The ICSI technique has not only been applied to rescue infertile male strains but also to produce transgenic rats. The optimal DNA concentration for the ICSI-tg method (0.1 to 0.5 μg/ml) is lower than that for the conventional pronuclear microinjection. Production efficiency was improved when the ...
The fears and concerns. Powerful tools can create or destroy as well as have unintended consequences. CRISPR/Cas9 could potentially be used to edit germ cells or embryos, thus changing an organisms entire genetic heritage. Some researchers are looking to impose regulations or some sort of moratorium so that the technology wouldnt be used to create "designer babies." Last April, Chinese researchers reported doing modifications to non-viable human embryos that stirred geneticists in other countries to call for a slowdown in this kind of work.. Others worry about an application of the technology called gene drives - genes engineered to break normal rules of inheritance so that changes get passed across generations. Gene drives have the potential of modifying mosquitoes, for example, in such a way that diseases like malaria could be eliminated entirely, but could rogue gene drives have unexpected consequences? Could bacteria or viruses, for example, pick up gene drives, and pass them around the ...
One aspect of research in our laboratory is directed toward a detailed understanding of the molecular mechanisms by which vertebrate organisms develop from single-celled embryos into complex organisms. This research utilizes zebrafish as a model organism. Advantages of the zebrafish include fecundity, an optically clear, rapidly developing embryo, and the opportunity to experimentally manipulate fertilization and development so as to produce parthenogenetic or haploid offspring. In addition, a full genomic sequence is available. A technique of central importance is the production of transgenic zebrafish via the direct microinjection of cloned genes into fish embryos. Transgenic zebrafish possessing recombinant gfp and rfp marker genes are being generated for a variety of purposes, including 1) basic research into recombination mechanisms and transgenesis strategies, 2) the study of transgene inheritance patterns, and 3) the analysis of altered gene expression and its phenotypic ...
This is a photograph of a transgenic rabbit named Alba who has a jellyfish gene allowing it to glow a bright green. The green fluorescent protein (GFP)is characteristic of the Pacific Northwest jellyfish and through genetic transfer has also become a characteristic of Albas phenotype. Under the correct lighting conditions, the green glow is visible ...
Transgenesis is the process of introducing an exogenous gene-called a transgene-into a living organism so that the organism will exhibit a new property and transmit that property to its offspring. Transgenesis can be facilitated by liposomes, enzymes, plasmid vectors, viral vectors, pronuclear injection, protoplast fusion, and ballistic DNA injection. Transgenesis can occur in nature. Transgenic organisms are able to express foreign genes because the genetic code is similar for all organisms. This means that a specific DNA sequence will code for the same protein in all organisms. Due to this similarity in protein sequence, scientists can cut DNA at these common protein points and add other genes. An example of this is the "super mice" of the 1980s. These mice were able to produce the human protein tPA to treat blood clots. The most common type of transgenesis research is done with bacteria and viruses which are able to replicate foreign DNA. The plasmid DNA is cut using restriction enzymes, ...
Accreditation: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.. Credit: The University of Florida College of Medicine designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.. Release Date: February 11, 2016. Expiration Date: February 11, 2017. ...
TT2013, will be held in Guangzhou/ Canton, P.R. China, on February 25-27, 2013, immediately after the Chinese New Year festival, at the Baiyun International Convention Center. The TT2013 meeting is organized by Professor Ming Zhao from Southern Medical University, Guangzhou. Following the meeting, a 3-day workshop about hands-on practical technicals will take place in Sun Yat-Sen University, Guangzhou (February 28 - March 2). Professor Wenhao Xu , director of Gene Targeting and Transgenic Facility, University of Virginia, will give the lectures on piezo injection, laser-assisted application, mouse colony management, etc ...
The CARD-Texas Mouse Reproductive Technology Workshop was held on November 14th-18th 2017 at the Texas A&M Institute for Genomic Medicine (TIGM) in College Station, Texas. The workshop was organized by Naomi Nakagata and Toru Takeo of the Center for Animal Resources and Development (CARD) at Kumamoto University, Andrei Golovko and Benjamin Morpurgo of TIGM, Jan Parker-Thornburg of The University of Texas M.D. Anderson Cancer Center, and William Shawlot of The University of Texas at Austin. Nineteen students and seventeen instructors and lecturers participated in the five-day lecture and hands-on workshop. The first day of the workshop began with welcoming remarks by Bill McCutchen, Executive Associate Director of Texas A&M AgriLife Research, and Ben Morpurgo, Executive Director of TIGM. This was followed by a series of morning lectures. Professor Nakagata gave an overview of cryopreservation in mice and a history of the mouse cryopreservation course. Jorge Sztein, Visiting Professor of CARD, ...
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
The report, entitled "Xenotransplantation of Transgenic Pig Myelin Forming Cells Promotes Axonal Regeneration and Restores Conduction Across the transected spinal cord," is based on research conducted in the laboratories of Dr. Jeffrey D. Kocsis of the Department of Neurology, Yale University School of Medicine, and Dr. William L. Fodor, Senior Director of Xenotransplantation at Alexion Pharmaceuticals, Inc. and their colleagues. ...
A research team at the Northeast Agricultural University in Harbin managed to breed three transgenic pigs by injecting fluorescent green protein and a "bunch of other junk" into embryonic pigs, said Professor Liu Zhonghua. Liu wore a fancy white lab coat and had multiple degrees adorning his walls, so we assume he must be pretty smart ...
WHICH TRANSGENIC PIG WILL BE USED FOR ISLET TRANSPLANTATION IN HUMANS? (NHMRC/JDRF Special Program Grants in Type 1 Diabetes) awarded by NHMRC 2007 - 2013 ...
FACT SHEETS Video crew at Hematech, Inc. Collection of human polyclonal antibodies from a cloned transgenic steer by plasmapheresis, a procedure used with human patients.The public experience with animal...
The proteins involved and differentially expressed in the early response of the endothelial cell to irradiation are studied by broad-spectrum methods (proteomic analysis) to model the response and characterise the essential participants playing a role in initiation and progression of the pathological phenotype. This approach via the biology of complex systems will allow an initial model of the endothelial response to irradiation and the persistence of its dysfunction to be obtained. Subsequently, the correlation explored between early biological effects and later biological effects will be validated in vivo by conventional radiopathology approaches involving innovative preclinical transgenic animal models. Study of the in vivo contribution of the vascular compartment in initiation and progression of radiation-induced lesions is in fact confronted with a technological barrier. The possibility of switching off a gene in a specific cellular compartment with the Cre-lox technology opens new ...
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Genesee the Drosophila App provides users with a quick reference to a variety of Drosophila melanogaster mutants. Users can access mutant images and descriptions and can easily link to www.flybase.org for complete and [GB]
Schematic representation of the δ deletion transgenic constructs. (a) Map of TG1. The vertical bars represent cloning sites in the construction of TG1 (21). (
Prolyl 4-hydroxylase (P4H) is a heterotetramer enzyme consisting of alpha-subunits (P4Halpha) and beta-subunits (P4Hbeta), and is required for collagen biosynthesis. Previously, we generated transgenic silkworms that produced human type III collagen fragments (mini-collagens) in the posterior silk gland (PSG). However, prolyl 4-hydroxylation did not occur on the mini-collagens, because in spite of an abundant expression of P4Hbeta in PSGs, P4Halpha expression was quite low there, thus resulting in an insufficient activity of P4H. In this study we aimed at generating hybrid transgenic silkworms whose PSGs are capable of producing mini-collagens and enough P4H for their prolyl 4-hydroxylation. Isolated PSGs were bombarded with fibroin L-chain gene promoter-driven vectors containing Bombyx mori P4Halpha (BmP4Halpha) cDNAs and were transplanted into the hemolymphatic cavity. The P4H activity in the PSG cells significantly increased, indicating that the expressed BmP4Halpha formed active tetramers with
To date, unequivocal neuroanatomical features have been demonstrated neither for sporadic nor for familial schizophrenia. Here, we investigated the neuroanatomical changes in a transgenic rat model for a subset of sporadic chronic mental illness (CMI), which modestly overexpresses human full-length, non-mutant Disrupted-in-Schizophrenia 1 (DISC1), and for which aberrant dopamine homeostasis consistent with some schizophrenia phenotypes has previously been reported. Neuroanatomical analysis revealed a reduced density of dopaminergic neurons in the substantia nigra and reduced dopaminergic fibres in the striatum. Parvalbumin-positive interneuron occurrence in the somatosensory cortex was shifted from layers II/III to V/VI, and the number of calbindin-positive interneurons was slightly decreased. Reduced corpus callosum thickness confirmed trend-level observations from in vivo MRI and voxel-wise tensor based morphometry. These neuroanatomical changes help explain functional phenotypes of this ...
Nonsyndromic hearing loss (NSHL) is of great clinical importance, and mutations in the GJB2 gene and the encoded human CONNEXIN 26 (CX26) protein play important roles in the genetic pathogenesis. The CX26 p.R184Q mutation was shown to be a dominant-negative effect in our previous study. Previously, we also demonstrated that zebrafish Cx30.3 is orthologous to human CX26. In the present study, we established transgenic zebrafish models with mutated Cx30.3 specifically expressed in the supporting cells of zebrafish inner ears driven by the agr2 promoter, to demonstrate and understand the mechanism by which the human CX26 R.184 mutation causes NSHL. Our results indicated that significant structural changes in the inner ears of transgenic lines with mutations were measured and compared to wild-type zebrafish. Simultaneously, significant alterations of transgenic lines with mutations in swimming behavior were analyzed with the zebrafish behavioral assay. This is the first study to investigate the functional
Aktogen Limited is a Cambridge University start-up company founded in 2003 by Dr. Zoltan Asztalos who has more than fifteen years experience in fruit fly behaviour genetics.. Aktogen offers behaviour and genetic services for fruit fly, Drosophila melanogaster laboratories, as well as pharmaceutical companies.. Aktogen has particular experience in behaviour tests from as simple as locomotion to learning and memory measurements.. The company also offers services to generate transgenic Drosophila strains, including making custom designed genetic constructs and embryo transformation.. Aktogen aims to accelerate the discovery of drug targets and drugs for the treatment of human CNS disorders. Drosophila offers a wealth of genetic tools and complex behaviour for the identification of the inherited components of CNS disorders. Aktogen has an edge in developing automated fruit fly behaviour systems to effectively test complex behaviour (e.g. non-associative learning, habituation and sensitization) that ...
Mutations in the human Mid1 gene cause Opitz G/BBB syndrome, which is characterized by various midline closure defects. The Caenorhabditis elegans homolog of Mid1, madd-2, positively regulates signaling by the unc-40 Netrin receptor during the extension of muscle arms to the midline and in axon guidance and branching. During uterine development, a specialized cell called anchor cell (AC) breaches the basal laminae separating the uterus from the epidermis and invades the underlying vulval tissue. AC invasion is guided by an UNC-6 Netrin signal from the ventral nerve cord and an unknown guidance signal from the vulval cells. Using genetic epistasis analysis, we show that madd-2 regulates AC invasion downstream of or in parallel with the Netrin signaling pathway. Measurements of AC shape, polarity and dynamics indicate that MADD-2 prevents the formation of ectopic AC protrusions in the absence of guidance signals. We propose that MADD-2 represses the intrinsic invasive capacity of the AC, while the ...