Cross-breeding of Gunn and LA Wistar rats which have deficiencies in different isoforms of UDP-glucuronosyltransferases

我们发现了一种突变的Wistar大鼠品系（LA Wistar大鼠），它有一个缺陷的雄酮UDP-葡萄糖醛酸转移酶（GT）的活性。随后，我们选择并有近交LA Wistar大鼠。对大鼠GT异构体的生物化学研究已经广泛进行，并且基于GT异构体的纯化及其cDNA的克隆，在大鼠肝脏中似乎存在六种或更多种GT异构体。然而，对GT基因家族的染色体结构知之甚少。为了阐明GT基因的连锁关系，我们将LA Wistar大鼠与胆红素GT缺乏的古恩大鼠杂交，然后在两年的科学研究补助金中进行兄妹近交。用部分肝切除法测定了F1和F2代肝脏对胆红素、雄酮和4-硝基酚的GT活性，结果表明F1代对三种底物的GT活性均正常。在F2代，胆红素和雄激素有4种不同组合 关于我们 一个GT活动。这些组合是两种GT活性的缺陷，胆红素或雄酮GT活性的单一缺陷和两种正常GT活性。它们以大约1：3：3：9的比例分离。这一比例与孟德尔的独立分类原则相一致，并提供了胆红素GT和雄甾酮GT基因位于不同染色体上的证据。在F2代中，低的4-硝基酚GT和缺陷的胆红素GT活性没有分离，因此表明这些突变的GT基因位于同一染色体上。本研究中使用的古恩大鼠头部有黑色色素，背部有黑色条纹（带帽），而LA Wistar大鼠是白化病。所有的F1杂种表现出类似于古恩大鼠的毛色。在F2代中，在这四个组中发现了蒙面和白化病大鼠，并以约3：1的比例进行隔离。本研究首次证实了大鼠的白化大衣色基因与胆红素和雄甾酮GT基因之间存在遗传连锁。对GT基因家族的染色体定位及GT亚型缺失的分子机制有待进一步研究。少

We discovered a mutant Wistar rat strain (LA Wistar rats) which has a defect in androsterone UDP-glucuronosyltransferase (GT) activity. Subsequently, we selected and have inbred LA Wistar rats. Biochemical studies on rat GT isoforms have been extensively carried out and six or more GT isoforms appear to exist in the rat liver, based on the purification of GT isoforms and the cloning of their cDNAs. However, very little is known about the chromosomal organization of GT gene family. To clarify the linkage relationships for GT genes, we crossed LA Wistar rats with Gunn rats,which have deficiency in bilirubin GT, followed by brother-sister inbreeding in two years of this Grant-in Aid for Scientific Research. Hepatic GT activities toward bilirubin, androsterone and 4-nitrophenol were assayed by partial hepatectomy of F1 and F2 offsprings.All the F1 hybrids showed normal GT activities toward three substrates. in F2 generation, there were four different combinations of bilirubin and androster … More one GT activities. These combinations were defects in both GT activities, a single defect in bilirubin or androsterone GT activity and two normal GT activities. They were segregated in the approximate ratio of 1:3:3:9. This ratio is consistent with Mendel's Principle of Independent Assortment, and provides evidence that bilirubin GT and androsterone GT genes are located on different chromosomes. In F2 generation, low 4-nitrophenol GT and defective bilirubin GT activities were not segregated, consequently indicating that these mutant GT genes are located on the same chromosome.Gunn rats used inthis study have black pigment on their heads and a black stripe on their backs (hooded), whereas LA Wistar rats are albino. All the F1 hybrids showed a coat color similar to that of Gunn rats. In the F2 generation, hooded and albino rats were found in these four groups and were segregated in the approximate ratio of 3:1. These results provide evidence that albinocoat-color gene is not linked with bilirubin and androsterone GT genes.This study is the first demonstration of the genetic linkage of GT genes in the rat. Further study id tequired to elucidate the chromosomal localization of the GT gene family and the molecular mechanism of the deficiency in GT isoforms. Less