Kershaw E E, Chua S C, Williams J A, Murphy E M, Leibel R L
Laboratory of Human Behavior and Metabolism, Rockefeller University, New York, New York 10021, USA.
Genomics. 1995 May 1;27(1):149-54. doi: 10.1006/geno.1995.1017.
Recessive mutations at the rat fatty locus (fa, facp), which produce obesity, insulin resistance, and diabetes, provide useful experimental models for similar phenotypes in humans. The molecular pathogenesis of the metabolic phenotype in animals segregating for fa is unknown and difficult to study once the confounding metabolic effects of obesity are present. Although various experimental methods distinguish preobese from lean rats (phenotypic markers and molecular markers genetically linked to fatty), technical difficulties limit their utility. We report the identification of two (GT)n simple sequence repeats (SSRs) near the rat phosphoglucomutase gene (Pgm1) gene and two SSRs, (GA)n and (GT)n, near the rat complement component 8 beta gene (C8b). These SSRs map to an approximately 4-cM interval flanking the fatty locus on rat chromosome 5. Use of these molecular markers in combination offers an improved method for early assessment of gene dosage for fa and hence for studying the fundamental molecular physiology underlying the derangements of metabolism and behavior resulting from mutations in this gene.
大鼠脂肪位点（fa、facp）的隐性突变会导致肥胖、胰岛素抵抗和糖尿病，为人类的类似表型提供了有用的实验模型。对于携带fa等位基因的动物，其代谢表型的分子发病机制尚不清楚，而且一旦肥胖产生混杂的代谢效应，就很难进行研究。尽管各种实验方法可区分肥胖前期大鼠和瘦大鼠（与脂肪基因相关的表型标记和分子标记），但技术难题限制了它们的实用性。我们报告了在大鼠磷酸葡萄糖变位酶基因（Pgm1）附近鉴定出两个（GT）n简单序列重复（SSR），以及在大鼠补体成分8β基因（C8b）附近鉴定出两个SSR，即（GA）n和（GT）n。这些SSR定位于大鼠5号染色体上脂肪位点两侧约4厘摩的区间。联合使用这些分子标记提供了一种改进的方法，可用于早期评估fa的基因剂量，从而研究该基因突变导致的代谢和行为紊乱背后的基本分子生理学。
