Department of Pediatrics, University of California, Davis, California 95616, USA.
Physiol Genomics. 2012 Nov 1;44(21):1052-62. doi: 10.1152/physiolgenomics.00134.2011. Epub 2012 Sep 11.
Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUC-Lepr (faSte) (ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-(D1Rat42-D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation (Lepr (faSte)) (P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC Lepr (faSte). Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function.
在 BN/Crl（BN）×ZUC-Lepr（faSte）（ZUC）回交的后代中进行连锁作图，鉴定出尿白蛋白排泄（UAE）的雄性特异性数量性状位点（QTL）位于大鼠 1 号染色体上。产生了一个纯合 ZUC.BN-（D1Rat42-D1Rat90）/Ste 同基因系，该系在 ZUC 背景上含有来自 1 号染色体 135 到 276Mb 的 BN 供体等位基因。当两个系都为 ZUC 瘦素受体脂肪突变（Lepr（faSte））纯合子时，我们观察到 15 周龄 Zucker 背景品系雄性的尿白蛋白与肌酐比值（ACR）是同性别和同年龄同基因系动物的三倍（P<0.0001）。然后，我们在供体区域内进行了连锁作图，没有受到其他染色体的混杂影响。在由同时携带 BN 供体区域和 ZUC Lepr（faSte）杂合的父母杂交产生的 248 只 F2 雄性大鼠群体中收集了表型。在六个肾脏性状中，Lepr 基因型与 1 号染色体 QTL 之间观察到显著的相互作用：尿量、10 和 15 周时的 UAE、ACR、右肾重量和血浆尿素氮。一些性状，如 UAE 和 ACR，在染色体的远端表现出第二个峰值。肾盂积水表现出一个或两个 QTL，取决于对体重的调整。结果现在证明了至少两组具有不同相关性的并发性状与肾功能有关。
