Faculty Research 1990 - 1999
Hyperleptinemia and leptin receptor variant Asp600Asn in the obese, hyperinsulinemic KK mouse strain.
Document Type
Article
Publication Date
1998
Keywords
Amino-Acid-Sequence, Animal, Base-Sequence, Carrier-Proteins: ge, Crosses-Genetic, DNA-Primers: ge, DNA-Complementary: ge, Female, Insulin, Male, Mice, Mice-Inbred-C57BL, Mice-Mutant-Strains, Mice-Obese, Microsatellite-Repeats, Molecular-Sequence-Data, Polymerase-Chain-Reaction, Proteins: me, Sequence-Homology-Amino-Acid, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Variation-(Genetics)
First Page
337
Last Page
345
JAX Source
J Mol Endocrinol 1998 Dec;21(3):337-45
Grant
DK50692/DK/NIDDK, CA34196/CA/NCI
Abstract
KK obese mice exhibit a multigenic syndrome of moderate obesity, hyperinsulinemia and hyperglycemia. Here we show that the syndrome is accompanied by a marked elevation of leptin protein in adipose tissue, as well as leptin levels in serum, which corresponds with the degree of obesity. The cDNA sequence of leptin is normal in KK mice, whereas three nucleotide polymorphisms were found in the cDNA of the leptin receptor, one of them resulting in exchange of an aspartate residue for asparagine (Asp600Asn) in a highly conserved part of the second extracellular cytokine-receptor homology module. In female (but not male) F2 mice of a C57BL/6JxKK intercross, the weight of gonadal, retroperitoneal and mesenteric adipose tissue was positively correlated with the number of alleles inherited from the KK parental strain at a microsatellite marker (D4Mit175) which maps close (0.7 centimorgan proximal) to the leptin receptor gene. It is suggested that the Asp600Asn leptin receptor variant contributes to the obesity syndrome in KK female mice, but that its contribution is only a part of the multigenic syndrome.
Recommended Citation
Igel M,
Taylor BA,
Phillips SJ,
Becker W,
Herberg L,
Joost HG.
Hyperleptinemia and leptin receptor variant Asp600Asn in the obese, hyperinsulinemic KK mouse strain. J Mol Endocrinol 1998 Dec;21(3):337-45