Igel M, Taylor B A, Phillips S J, Becker W, Herberg L, Joost H G
Institut für Pharmakologie und Toxikologie, Aachen, Germany.
J Mol Endocrinol. 1998 Dec;21(3):337-45. doi: 10.1677/jme.0.0210337.
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.
KK肥胖小鼠表现出中度肥胖、高胰岛素血症和高血糖的多基因综合征。我们在此表明，该综合征伴随着脂肪组织中瘦素蛋白以及血清中瘦素水平的显著升高，这与肥胖程度相对应。KK小鼠中瘦素的cDNA序列正常，而在瘦素受体的cDNA中发现了三个核苷酸多态性，其中一个导致在第二个细胞外细胞因子受体同源模块的高度保守部分中，天冬氨酸残基被天冬酰胺取代（Asp600Asn）。在C57BL/6J×KK杂交的雌性（而非雄性）F2小鼠中，性腺、腹膜后和肠系膜脂肪组织的重量与在一个微卫星标记（D4Mit175）处从KK亲本菌株遗传的等位基因数量呈正相关，该微卫星标记位于靠近（近端0.7厘摩）瘦素受体基因的位置。提示Asp600Asn瘦素受体变体促成了KK雌性小鼠的肥胖综合征，但其作用只是多基因综合征的一部分。
