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| Genetic modifiers of Lepr(fa) associated with variability in insulin production and susceptibility to NIDDM |
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| Author(s): Chung WK, Zheng M, Chua M, Kershaw E, PowerKehoe L, Tsuji M, WuPeng XS, Williams J, Chua SC, Leibel RL |
| Source: GENOMICS Volume: 41 Issue: 3 Pages: 332-344 Published: MAY 1 1997 |
| Times Cited: 48 References: 60 |
| Abstract: In an attempt to identify the genetic basis for susceptibility to non-insulin-dependent diabetes mellitus within the context of obesity, me generated 401 genetically obese Lepr(fa)/Lepr(fa) F2 WKY13M intercross rats that demonstrated wide variation in multiple phenotypic measures related to diabetes, including plasma glucose concentration, percentage of glycosylated hemoglobin, plasma insulin concentration, and pancreatic islet morphology. Using selective genotyping genome scanning approaches, me have identified three quantitative trait loci (QTLs) on Chr. 1 (LOD 7.1 for pancreatic morpholology), Chr. 12 (LOD 5.1 for body mass index and LOD 3.4 for plasma glucose concentration), and Chr. 16 (P < 0.001 for genotype effect on plasma glucose concentration). The obese F2 progeny demonstrated sexual dimorphism for these traits, with increased diabetes susceptibility in the males appearing at approximately 6 weeks of age, as sexual maturation occurred. For each of the QTLs, the linked phenotypes demonstrated sexual dimorphism (more severe affection in males). The QTL on Chr. 1 maps to a region vicinal to that previously linked to adiposity in studies of diabetes susceptibility in the nonobese Goto-Kakizaki rat, which is genetically closely related to the Wistar counterstrain we employed. Several candidate genes, including tubby (tub), multigenic obesity I (Mob1), adult obesity and diabetes (Ad), and insulin-like growth factor-2 (Igf2), map to murine regions homologous to the QTL region identified on rat Chr. 1. (C) 1997 Academic Press. |
| Document Type: Article |
| Language: English |
Addresses:
1. ROCKEFELLER UNIV, HUMAN BEHAV & METAB LAB, NEW YORK, NY 10021 USA
2. VASSAR COLL, DEPT BIOL, ANIM MODEL CORE LAB, NIH, POUGHKEEPSIE, NY 12601 USA |
| Publisher: ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 |
| Subject Category: Biotechnology & Applied Microbiology; Genetics & Heredity |
| IDS Number: WX153 |
| ISSN: 0888-7543 |
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