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

具有不同 UDP-葡萄糖醛酸基转移酶亚型缺陷的 Gunn 和 LA Wistar 大鼠的杂交

基本信息

批准号：
62570996
负责人：
MATSUI Michio
金额：
$ 1.41万
依托单位：
Kyoritsu College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

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

我们发现了一株突变Wistar大鼠（LA Wistar大鼠），其雄酮udp -葡萄糖醛酸转移酶（GT）活性存在缺陷。随后，我们选择并近交了LA Wistar大鼠。对大鼠GT异构体的生化研究已经广泛开展，基于GT异构体的纯化及其cdna的克隆，大鼠肝脏中似乎存在6种或更多的GT异构体。然而，对GT基因家族的染色体结构了解甚少。为了明确GT基因的连锁关系，我们将胆红素GT缺乏的LA Wistar大鼠与Gunn大鼠杂交，并在本科研资助项目的两年内进行了兄妹近亲繁殖。采用部分肝切除法测定F1和F2子代小鼠肝脏GT对胆红素、雄酮和4-硝基酚的活性。所有F1杂交种对3种底物均表现出正常的GT活性。在F2代，有4种不同的胆红素和雄激素组合。这些组合都有GT活性缺陷，胆红素或雄酮GT活性单一缺陷和两个正常GT活性。他们按大约1:3:3:9的比例被分开。这一比例符合孟德尔的独立配种原理，并提供了胆红素GT和雄酮GT基因位于不同染色体上的证据。在F2代中，低4-硝基酚GT和有缺陷胆红素GT活性的基因没有分离，这表明这些突变的GT基因位于同一染色体上。在这项研究中使用的Gunn大鼠头部有黑色色素，背部有黑色条纹（带帽），而LA Wistar大鼠是白化的。所有F1杂交种的毛色都与Gunn大鼠相似。F2代四组均有褐斑大鼠和白化大鼠，按3:1的比例进行分离。这些结果提供了白化衣色基因与胆红素和雄酮GT基因无关的证据。本研究首次证实了GT基因在大鼠体内的遗传连锁。需要进一步的研究来阐明GT基因家族的染色体定位和GT亚型缺乏的分子机制。少