Development of insulin resistance and hyperphagia in Zucker fatty rats.

The onset of hyperphagia in the Zucker fatty (fa/fa) rat occurs on a single day in postnatal development and could be driven by an increase in insulin sensitivity. To test this hypothesis, we performed insulin tolerance tests at several points in development. In rapidly growing juvenile rats, fatty rats are as insulin sensitive as lean rats at 4 wk of age but become increasingly insulin resistant as they became obese.

Effects of fatty (fa) allele and high-fat diet on adipose tissue leptin and lipid metabolism.

Leptin is an adipocyte-secreted hormone that binds hypothalamic receptors and potently decreases food intake. Leptin receptor defects in homozygous mutant Zucker fatty ( fa/fa) rats lead to massive obesity, hyperphagia, decreased energy expenditure, and insulin resistance, while the phenotype of heterozygous ( Fa/fa) lean rats lies between lean ( Fa/Fa) and obese ( fa/fa) rats. Whether heterezygotes exhibit specific changes in lipid metabolism in a diet-responsive manner is not clear.

[Effects of ob genotype on early development in mice].

Objective: To study the effects and the extent of dominance of ob gene on early development in mice.

Methods: ob genotypes, wild type (+/+), hybrid type (ob/+) and mutant type (ob/ob), were detected by polymerase chain reaction and restrict endonuclease technique. Body weight of mice was recorded daily for the first seventh weeks of life.

A developmental switch affecting growth of fatty rats.

Fatty (fa/fa) rats accumulate more adipose mass than their littermates soon after birth, but they first appear obese during the fourth week of life. We analyzed the effects of fa genotype on growth of pups housed with their dams through 4 wk of age. The fa genotype effects on daily gain were undetectable from 7 to 22 days of age but became highly significant (P = 10(-18)) at 23 days of age.

Eradication of infection with Helicobacter spp. by use of neonatal transfer.

Background And Purpose: Efficient methods for detection and elimination of Helicobacter spp. infections are needed to facilitate the development of Helicobacter-free mouse colonies. We developed an inexpensive, high-throughput method for preparation of fecal DNA for Helicobacter polymerase chain reaction (PCR) assays.

Misty (m) affects growth traits.

The misty (m) coat color mutation is commonly maintained in linkage disequilibrium with the obesity mutation diabetes (Leprdb) to serve as a marker for Leprdb genotype. Comparisons among Leprdb genotypes are made under the untested assumption that m has no effects on traits under investigation. We tested this assumption in a population segregating m in the absence of db.

ELISA detection of restriction site polymorphisms in the pig ryanodine receptor locus.

We compare two strategies for ELISA detection of restriction site polymorphisms (EDRSP) that are suitable for high-throughput genotyping of the pig ryanodine receptor point mutation (RYR1(hal)). In both procedures, target DNA is amplified by PCR with one primer that is 5' biotinylated and a second primer that is 5' fluoresceinylated. PCR products are captured in duplicate wells on a streptavidin-coated, 96-well plate.

Dietary fat and sex modify heterozygote effects of the rat fatty (fa) allele.

Rats carrying one copy of the obesity gene fa may exhibit intermediate phenotypes between lean (+/+) and homozygous mutants (fa/fa). Previous data suggested to us that fa heterozygotes may be more sensitive than wild-type rats to high fat diets. To test this hypothesis, we generated +/+ and fa/+ rats and fed them diets containing 12% or 48% energy as fat for 7 wk.

A rat homolog of the mouse deafness mutant jerker (je).

An autosomal recessive deafness mutant was discovered in our colony of Zucker (ZUC) rats. These mutants behave like shaker-waltzer deafness mutants, and their inner ear pathology classifies them among neuroepithelial degeneration type of deafness mutants. To determine whether this rat deafness mutation (-) defines a unique locus or one that has been previously described, we mapped its chromosomal location.

Quantitative analysis of abnormal spontaneous behavior and clinical assessment of the stargazer rat.

A new mutant derived from the Zucker rat strain called stargazer (homozygous stg/stg) displays abnormal behavior that is characterized by pronounced arching of the neck ("stargazing"), rapid circling, and conspicuous hyperactivity. Results of serologic assays performed by two independent diagnostic laboratories have indicated that the abnormal behavior in the stargazer is not the result of a viral or bacterial infection. In this report, different groups of stargazer rats and their normal-behaving littermates (heterozygous stg/+) were assessed with regard to spontaneous behaviors, heart rate, blood pressure, and plasma biochemical profiles.

Codominant effects of the fatty (fa) gene during early development of obesity.

Expression of a single copy of the rat obesity fatty (fa) gene may affect energy balance. To test this hypothesis, the effects of zero, one, and two copies of fa on early growth were evaluated, using a molecular genetic method for counting fa alleles inherited by 7- and 14-day-old F2 offspring of a BN/Crl x Crl:ZUC-fa F1 intercross. Litter and sex effects were controlled by multiple-regression analysis, allowing genotype effects on the weights of body, inguinal adipose pads, interscapular brown adipose tissue, and liver to be isolated.

Genetic map of rat chromosome 5 including the fatty (fa) locus.

Thirteen loci, including the obesity gene fatty (fa), were incorporated into a linkage map of rat Chromosome (Chr) 5. These loci were mapped in obese (fa/fa) progeny of a cross between BN x 13M-fal+F1 animals. Obese rats were scored for BN and 13M alleles at four loci (Ifna, D1S85h, C8b, and Lck1) by restriction fragment length polymorphisms and at eight additional loci (Glut1, Sv4j2, R251, R735, R980, R252, R371, and R1138) by simple sequence length polymorphisms (SSLP).

Stargazer (stg), new deafness mutant in the Zucker rat.

We describe a new deafness mutant found in the Zucker rat. The mutant phenotype appears to be caused by an autosomal recessive gene, tentatively named stargazer, gene symbol stg. The phenotype is characterized by stargazing, head tossing, drawing back, circling, and hyperactivity, all of which are apparent by the third week of life.

Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.

Loci linked to sensitivity to dietary obesity were identified by Quantitative Trait Locus (QTL) analysis of two mapping populations derived from a cross between AKR/J and SWR/J mice. AKR/J mice are sensitive to dietary obesity when fed a high fat diet while SWR/J mice are resistant. Intercrosses between these strains segregate the phenotype of sensitivity to dietary obesity.

Utility of a C-jun microsatellite marker in determining gene dosage for fatty (fa).

The Zucker fatty (fa) mutation provides a genetic model for obesity and non-insulin dependent diabetes mellitus. The molecular pathogenesis of the metabolic phenotype of these animals is not known. Detailed molecular maps of the region surrounding the fa locus on rat chromosome 5 can be used for positional cloning experiments as well as to permit genotyping of animals from appropriate crosses before the confounding metabolic effects of obesity have occurred.

The Zucker fatty (fa) gene is not a mutation of corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) appears to regulate several physiological systems that display prominent abnormalities in Zucker fatty (fa/fa) rats, including the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and feeding behavior. Moreover, central administration of CRF ameliorates the obese phenotype. In light of these observations, the gene for CRF is a plausible candidate for the defective gene in the Zucker fatty rat.

A molecular genetic method for genotyping fatty (fa/fa) rats.

After three decades of physiological research, the precise nature of the genetic lesion in Zucker fatty (fa/fa) rats remains unknown. Several methods have been used to identify preobese rats to detect the earliest phenotypic effects of the fa mutation. Most of these methods have used phenotypic characteristics that are not reliable until the second week of life, when increased adiposity is already evident.

Rat obesity gene fatty (fa) maps to chromosome 5: evidence for homology with the mouse gene diabetes (db).

The autosomal recessive mutations fa (rat) and db (mouse) cause obesity syndromes that develop early and ultimately become severe. Although both fa/fa rats and db/db mice have been studied extensively as models of human obesity and diabetes, the molecular bases of these phenotypes remain unknown. We have mapped fa in 50 fa/fa (obese) offspring of a (13M x Brown Norway) F1 fa/+ intercross relative to two molecular markers, Ifa and Glut-1, which flank db on mouse chromosome 4 and which are located on rat chromosome 5.