Solid tissues removed from ATM homozygous deficient mice do not exhibit a mutator phenotype for second-step autosomal mutations.
(17/904)
The presence of increased frequencies of blood-derived and solid tumors in ataxia-telangiectasia (A-T) patients, coupled with a role for the ATM (A-T mutation) protein in detecting specific forms of DNA damage, has led to the assumption of a mutator phenotype in A TM-deficient cells. Supporting this assumption are observations of increased rates of chromosomal aberrations and intrachromosomal homologous recombinational events in the cells of A-T patients. We have bred mice with knockout mutations for the selectable Aprt (adenine phosphoribosyltransferase) locus and the Atm locus to examine the frequency of second-step autosomal mutations in Atm-deficient cells. Two solid tissues were examined: (a) the ear, which yields predominately mesenchymal cells; and (b) the kidney, which yields predominately epithelial cells. We report here the lack of a mutator phenotype for inactivating autosomal mutations in solid tissues of the Atm-deficient mice. (+info)
The amphisbaenian ear: Blanus cinereus and Diplometopon zarudnyi.
(18/904)
Observations on the structure and function of the ear in amphisbaenians have been extended to two new species: to Blanus cinereus of the family Amphisbaenidae and Diplometopon zarudnyi of the family Trogonophidae. Blanus, considered one of the most primitive of this group of reptiles, shows a distinctive form of sound-receptive mechanism. The usual extracolumella is lacking, and the columella attaches to a cartilaginous plate beneath the skin posterior to the facial area. Diplometopon zarudnyi, a highly modified trogonophid, shows a columella and extracolumella of massive dimensions, with considerable calcification of the latter process. Cochlear potential measurements revealed the levels of auditory sensitivity in these species. A peculiar feature is the degree of stability of the ear's responses in the presence of large variations in body temperature. (+info)
Expression of DLX3 in chick embryos.
(19/904)
Higher vertebrates appear to possess six genes encoding a homeodomain of the distal-less type. We report the cloning and expression pattern of the chicken DLX3 gene, a homeobox gene highly related to the DLX5 gene with regard to both the encoded protein structure and the expression pattern. DLX3 RNA was observed during the development of the olfactory and otic placodes, in the distal portion of the first and second visceral arch mesenchyme, in the growing limb buds, and in the tail tip. No expression occurs in the central nervous system. (+info)
Evaluation of skin viscoelasticity and anisotropy by measurement of speed of shear wave propagation with viscoelasticity skin analyzer.
(20/904)
Skin viscoelasticity was evaluated by a fast, noninvasive assay based on the measurement of the speed of elastic shear wave propagation in the skin by a new portable and user-friendly viscoelasticity skin analyzer. The range of speed of elastic shear wave propagation measured by viscoelasticity skin analyzer allows the evaluation of the stiffness of a wide spectrum of artificial materials as well as the viscoelasticity of skin of laboratory animals and human subjects. The directional nature of the measurement enables to monitor the anisotropy of the materials tested. The speed of elastic shear wave propagation was shown to have a positive correlation with the stiffness of the material tested. In symmetric contralateral areas of intact skin in rabbit ears, similar viscoelasticity and anisotropy were observed. Twenty-four hours after the induction of local edema by croton oil, skin stiffness and anisotropy were significantly increased. In healthy human subjects of both sexes significant variations in skin stiffness and anisotropy were observed in three different skin areas along the forearms, but the speed of elastic shear wave propagation was similar in the symmetric contralateral areas. Age (17-65 y) seemed to have a limited effect on the viscoelasticity of the forearm skin. Hydrating creams decreased the stiffness of the forearm skin for only approximately 3 h. The stiffness and anisotropy of the skin of the breasts in female volunteers (20-86 y) increased with age, but the speed of elastic shear wave propagation was similar in symmetric contralateral areas in the same individuals. Based on these results, we propose the application of the viscoelasticity skin analyzer in experimental and clinical practice for quantitative evaluation of skin condition. (+info)
Stickler syndrome: further mutations in COL11A1 and evidence for additional locus heterogeneity.
(21/904)
Stickler syndrome (hereditary arthro-ophthalmopathy) is a dominantly inherited connective tissue disorder with ocular, oro-facial, auditory and skeletal manifestations. It is genetically and phenotypically heterogeneous with the majority of families having mutations in the gene encoding type II collagen (COL2A1) and exhibiting a characteristic 'membranous' or type 1 vitreous phenotype. More recently a novel mutation in the gene encoding the alpha1 chain of type XI collagen (COL11A1) was reported in a Stickler syndrome pedigree with a different 'beaded' or type 2 vitreous phenotype. In the present study five more families with the type 2 vitreous phenotype were examined for linkage to four candidate genes: COL2A1, COL5A2, COL11A1 and COL11A2. Two families were linked to COL11A1 and sequencing identified mutations resulting in shortened alphal(XI) collagen chains, one via exon skipping and the other via a multiexon deletion. One of the families showed weak linkage to COL5A2 but sequencing the open reading frame failed to identify a mutation. In the remaining two families all four loci were excluded by linkage analysis. These data confirm that mutations in COL11A1 cause Stickler syndrome with the type2 vitreous phenotype and also reveal further locus heterogeneity. (+info)
A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae.
(22/904)
Vaccinia virus (VV) proteins that interfere with the host response to infection are of interest because they provide insight into virus-host relationships and may affect the safety and immunogenicity of recombinant VV (rVV) vaccines. Such vaccines need assessment in animal models and with this aim a model of VV infection based on intradermal injection of BALB/c ear pinnae was developed and characterized. In this model, the outcome of infection is affected by the dose of virus inoculated but virus spread is minimal and the mice suffer no signs of systemic illness. Cellular and humoral immune responses to these infections were measured readily and were independent of virus dose over a 100-fold range. Thus the model seems suitable for the analysis of the safety and immunogenicity of VV mutants lacking specific immunomodulatory proteins or bearing foreign antigens. (+info)
Determination of the contribution of cysteinyl leukotrienes and leukotriene B4 in acute inflammatory responses using 5-lipoxygenase- and leukotriene A4 hydrolase-deficient mice.
(23/904)
Arachidonic acid metabolism by 5-lipoxygenase leads to production of the potent inflammatory mediators, leukotriene (LT) B4 and the cysteinyl LT. Relative synthesis of these subclasses of LT, each with different proinflammatory properties, depends on the expression and subsequent activity of LTA4 hydrolase and LTC4 synthase, respectively. LTA4 hydrolase differs from other proteins required for LT synthesis because it is expressed ubiquitously. Also, in vitro studies indicate that it possesses an aminopeptidase activity. Introduction of cysteinyl LT and LTB4 into animals has shown LTB4 is a potent chemoattractant, while the cysteinyl LT alter vascular permeability and smooth muscle tone. It has been impossible to determine the relative contributions of these two classes of LT to inflammatory responses in vivo or to define possible synergy resulting from the synthesis of both classes of mediators. To address this question, we have generated LTA4 hydrolase-deficient mice. These mice develop normally and are healthy. Using these animals, we show that LTA4 hydrolase is required for the production of LTB4 in an in vivo inflammatory response. We show that LTB4 is responsible for the characteristic influx of neutrophils accompanying topical arachidonic acid and that it contributes to the vascular changes seen in this model. In contrast, LTB4 influences only the cellular component of zymosan A-induced peritonitis. Furthermore, LTA4 hydrolase-deficient mice are resistant to platelet-activating factor, identifying LTB4 as one mediator of the physiological changes seen in systemic shock. We do not identify an in vivo role for the aminopeptidase activity of LTA4 hydrolase. (+info)
Persistence of infectious herpes simplex virus type 2 in the nervous system in mice after antiviral chemotherapy.
(24/904)
Young adult mice were inoculated with herpes simplex virus type 2 (HSV-2) in the ear pinna. A relatively severe infection resulted, and 45% of the mice died by 11 days postinfection. Therapy at 1 mg/ml by means of the drinking water with either famciclovir for periods of 5 or 10 days or valaciclovir for 5, 10, 15, or 20 days decreased clinical signs and reduced mortality to 15% or less. Throughout a period of 27 days, mice were tested daily for the presence of infectious virus in the ear pinna, brain stem, and ipsilateral trigeminal ganglia. Virus was cleared from these tissues in surviving, untreated animals by 12 days postinfection, and no infectious virus was detected subsequently in any tissue. Furthermore, no infectious virus was detected after day 9 in mice that had been treated with famciclovir. In mice that had received valaciclovir therapy, however, infectious virus was repeatedly detected in the trigeminal ganglia and brain stem tissue samples up to 7 days after treatment was discontinued. To date, no specific mechanism to account for these results has been discovered; however, possible mechanisms for the persistence of potentially infectious virus in neural tissue of treated mice are discussed. (+info)