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对反式氧化茋有活性的人类谷胱甘肽转移酶表达中的遗传差异是由一个基因缺失导致的。

Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion.

作者信息

Seidegård J, Vorachek W R, Pero R W, Pearson W R

机构信息

Department of Molecular Ecogenetics, Wallenberg Laboratory, University of Lund, Sweden.

出版信息

Proc Natl Acad Sci U S A. 1988 Oct;85(19):7293-7. doi: 10.1073/pnas.85.19.7293.

DOI:10.1073/pnas.85.19.7293
PMID:3174634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC282172/
Abstract

Glutathione transferase (GT; EC 2.5.1.18) mRNA levels were measured in human liver samples by using mouse and human cDNA clones that encode class-mu and class-alpha GT. Although all the RNA samples examined contained class-alpha GT mRNA, class-mu GT mRNA was found only in individuals whose peripheral leukocytes expressed GT activity on the substrate trans-stilbene oxide. The mouse class-mu cDNA clone was used to identify a human class-mu GT cDNA clone, lambda GTH411. The amino acid sequence of the GT encoded by lambda GTH411 is identical with the 23 residues determined for the human liver GT-mu isoenzyme and shares 76-81% identity with mouse and rat class-mu GT isoenzymes. The mouse and human class-mu GT cDNA inserts hybridize with multiple BamHI and EcoRI restriction fragments in the human genome. One of these hybridizing fragments is missing in the DNA of individuals who lack GT activity on trans-stilbene oxide. Hybridizations with nonoverlapping subfragments of lambda GTH411 suggest that there are at least three class-mu genes in the human genome. One of these genes appears to be deleted in individuals lacking GT activity on trans-stilbene oxide.

摘要

利用编码μ类和α类谷胱甘肽转移酶(GT;EC 2.5.1.18)的小鼠和人类cDNA克隆,检测了人类肝脏样本中GT的mRNA水平。尽管所有检测的RNA样本都含有α类GT mRNA,但仅在其外周血白细胞对反式氧化芪底物表现出GT活性的个体中发现了μ类GT mRNA。小鼠μ类cDNA克隆被用于鉴定一个人类μ类GT cDNA克隆,λGTH411。由λGTH411编码的GT的氨基酸序列与已确定的人类肝脏GT-μ同工酶的23个残基相同,并且与小鼠和大鼠的μ类GT同工酶具有76-81%的同一性。小鼠和人类μ类GT cDNA插入片段与人类基因组中的多个BamHI和EcoRI限制性片段杂交。在对反式氧化芪缺乏GT活性的个体的DNA中,这些杂交片段之一缺失。用λGTH411的非重叠亚片段进行杂交表明,人类基因组中至少有三个μ类基因。其中一个基因似乎在对反式氧化芪缺乏GT活性的个体中缺失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/0a11b1ceee0a/pnas00298-0263-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/4390ba0c2281/pnas00298-0261-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/b34948e9bc1e/pnas00298-0261-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/ce1da3099130/pnas00298-0261-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/0a11b1ceee0a/pnas00298-0263-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/4390ba0c2281/pnas00298-0261-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/b34948e9bc1e/pnas00298-0261-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/ce1da3099130/pnas00298-0261-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c8a/282172/0a11b1ceee0a/pnas00298-0263-a.jpg

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