Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

Techniques to alter a gene sequence that result in an inactivated gene, or one in which the expression can be inactivated at a chosen time during development to study the loss of function of a gene.

A family of the order Rodentia containing 250 genera including the two genera Mus (MICE) and Rattus (RATS), from which the laboratory inbred strains are developed. The fifteen subfamilies are SIGMODONTINAE (New World mice and rats), CRICETINAE, Spalacinae, Myospalacinae, Lophiomyinae, ARVICOLINAE, Platacanthomyinae, Nesomyinae, Otomyinae, Rhizomyinae, GERBILLINAE, Dendromurinae, Cricetomyinae, MURINAE (Old World mice and rats), and Hydromyinae.

Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)

Diseases of rodents of the order RODENTIA. This term includes diseases of Sciuridae (squirrels), Geomyidae (gophers), Heteromyidae (pouched mice), Castoridae (beavers), Cricetidae (rats and mice), Muridae (Old World rats and mice), Erethizontidae (porcupines), and Caviidae (guinea pigs).

Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region.

Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed)

The prevailing temper or spirit of an individual or group in relation to the tasks or functions which are expected.

Congenital fissure of the soft and/or hard palate, due to faulty fusion.

A genus of GRAM-POSITIVE ENDOSPORE-FORMING RODS, in the family Alicyclobacillaceae, containing a unique lipid in their membranes.

The interaction of persons or groups of persons representing various nations in the pursuit of a common goal or interest.

The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.

The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.

A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.

Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc.

Symptom of overactive detrusor muscle of the URINARY BLADDER that contracts with abnormally high frequency and urgency. Overactive bladder is characterized by the frequent feeling of needing to urinate during the day, during the night, or both. URINARY INCONTINENCE may or may not be present.

Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus.

Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.

A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.

Involuntary discharge of URINE that is associated with an abrupt and strong desire to void. It is usually related to the involuntary contractions of the detrusor muscle of the bladder (detrusor hyperreflexia or detrusor instability).

A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.

Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).

A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).

A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.

Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.

Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.

A hepatocyte nuclear factor that is closely related to HEPATOCYTE NUCLEAR FACTOR 1-ALPHA but is only weakly expressed in the LIVER. Mutations in hepatocyte nuclear factor 1-beta are associated with renal CYSTS and MATURITY-ONSET DIABETES MELLITUS type 5.

A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern.

PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.

A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.

Method in which repeated blood pressure readings are made while the patient undergoes normal daily activities. It allows quantitative analysis of the high blood pressure load over time, can help distinguish between types of HYPERTENSION, and can assess the effectiveness of antihypertensive therapy.

Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.

The number of times the HEART VENTRICLES contract per unit of time, usually per minute.

Techniques for measuring blood pressure.

An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.

A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.

The ability of the kidney to excrete in the urine high concentrations of solutes from the blood plasma.

Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.

Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).

Impaired conduction of cardiac impulse that can occur anywhere along the conduction pathway, such as between the SINOATRIAL NODE and the right atrium (SA block) or between atria and ventricles (AV block). Heart blocks can be classified by the duration, frequency, or completeness of conduction block. Reversibility depends on the degree of structural or functional defects.

A group of antigens consisting principally of Jk(a) and Jk(b), determined by allelic genes. Amorphs are encountered. Antibodies of these substances are usually weak and quite labile, stimulated by erythrocytes.