Date of Award

1998

Degree Name

Biological Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

E. Bowie Kahle

Second Advisor

Leonard J. Deutsch

Abstract

The LA/N-corpulent (cp) rat obesity model was a congenic rat strain developed at the National Institutes of Health by C. T. Hansen . The LA/N-cp rat originated from breeding the Koletsky rat, possessing the corpulent gene, with the normotensive LA/N inbred rat. The autosomal recessive single gene mutation, cp, produces obesity with hyperphagia, hyperinsulinemia and elevated activities of liver and skeletal muscle lipogenic enzymes in the LA/N-cp rat model. The Zucker-fatty mutation, which was mapped to rat chromosome , resulted in a comparable, but not identical obesity syndrome. Breeding experiments by Yen et al have suggested the cp and fa genes to be homologous and possibly allelic. To verify this hypothesis, we established interstrain crosses, LA/N-cp (cp/+) with 13M/Vc (fa/+), which yielded 10 obese and 32 lean offspring, a 1:3.2 ratio Our results support the cp -fa gene homology. For molecular analysis, crosses segregating the cp gene were constructed using a genetically distant counterstrain, Brown Norway (BN)/Crl (+/+) rats. Fourteen crosses between (LA/N-cp x BN) (cp/+) offspring yielded 31 obese and 80 lean progeny, a 1:2.6 ratio (=0.230, p>0.50). We have mapped the chromosomal location of cp in 30 obese (LA/N-cp x BN) progeny using microsatellite markers for two genes flanking the fatty locus: glucose transporter 1 (Glut1) and phosphoglucomutase 1 (Pgm1). PCR-amplified sequence polymorphisms detected four Brown Norway alleles (representing 4 crossovers) at the Glut1 locus and 1 BN allele at the Pgm1 locus in 60 meioses. Our results place the cp mutation on rat chromosome 5, flanked by Glut1 and Pgm1. Pgm1 — 1.67 centiMorgan (cM) —— 6.67 cM — Glut1. With the proposed homology verified through our complementation studies, our physical mapping supports cp and fa as mutations in the same gene . Thus, the new symbol is now the proper designation for the obese syndrome, corpulent (cp).

Subject(s)

Obesity – Research.

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