The granzyme B gene is highly polymorphic in wild mice but essentially invariant in common inbred laboratory strains.

Kevin Y T Thia, Joseph A Trapani
{"title":"The granzyme B gene is highly polymorphic in wild mice but essentially invariant in common inbred laboratory strains.","authors":"Kevin Y T Thia,&nbsp;Joseph A Trapani","doi":"10.1111/j.1399-0039.2007.00872.x","DOIUrl":null,"url":null,"abstract":"<p><p>Granzyme B is a 247 amino acid pro-apoptotic protease secreted by effector lymphocytes for the purpose of killing virus-infected cells. While the capacity of granzyme B to potently induce caspase-dependent apoptosis has long been recognized, it has only recently been found that human and mouse granzyme B activate overlapping but distinct apoptotic pathways. To investigate a possible evolutionary basis for this observation, we sequenced the exons and flanking intronic sequences of the mouse Gzmb gene from a variety of inbred laboratory strains and wild mice. The sequences of 12/13 inbred strains encoded identical proteins, the exception being DBA/2, whose sequence varied at two amino acids. By contrast with the laboratory strains, there was extensive polymorphism in the Gzmb gene of 54 wild mice and 28 wild-derived inbred mice examined, resulting in 2-18 amino acid differences in the predicted proteins, a discrepancy rate of up to 7.3%. Many of these amino acid variations were found in rat and/or human granzyme B. The granzyme B allotype of inbred laboratory strains could be identified in only one of three geographically dispersed clans of wild mice and was absent from all 28 wild-derived inbred strains. The Gzmb gene of Mus musculus castaneus, a close relative of laboratory mice, encoded six amino acid differences compared with the laboratory strains, all of which were also found in corresponding positions in the granzyme B molecules of wild mice. Unlike the protease, the extended granzyme B recognition and cleavage site in Bid, a key pro-apoptotic substrate, was invariant.</p>","PeriodicalId":23105,"journal":{"name":"Tissue antigens","volume":"70 3","pages":"198-204"},"PeriodicalIF":0.0000,"publicationDate":"2007-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1399-0039.2007.00872.x","citationCount":"20","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue antigens","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/j.1399-0039.2007.00872.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 20

Abstract

Granzyme B is a 247 amino acid pro-apoptotic protease secreted by effector lymphocytes for the purpose of killing virus-infected cells. While the capacity of granzyme B to potently induce caspase-dependent apoptosis has long been recognized, it has only recently been found that human and mouse granzyme B activate overlapping but distinct apoptotic pathways. To investigate a possible evolutionary basis for this observation, we sequenced the exons and flanking intronic sequences of the mouse Gzmb gene from a variety of inbred laboratory strains and wild mice. The sequences of 12/13 inbred strains encoded identical proteins, the exception being DBA/2, whose sequence varied at two amino acids. By contrast with the laboratory strains, there was extensive polymorphism in the Gzmb gene of 54 wild mice and 28 wild-derived inbred mice examined, resulting in 2-18 amino acid differences in the predicted proteins, a discrepancy rate of up to 7.3%. Many of these amino acid variations were found in rat and/or human granzyme B. The granzyme B allotype of inbred laboratory strains could be identified in only one of three geographically dispersed clans of wild mice and was absent from all 28 wild-derived inbred strains. The Gzmb gene of Mus musculus castaneus, a close relative of laboratory mice, encoded six amino acid differences compared with the laboratory strains, all of which were also found in corresponding positions in the granzyme B molecules of wild mice. Unlike the protease, the extended granzyme B recognition and cleavage site in Bid, a key pro-apoptotic substrate, was invariant.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
颗粒酶B基因在野生小鼠中高度多态性,但在常见的近交实验室菌株中基本不变。
颗粒酶B是一种247个氨基酸的促凋亡蛋白酶,由效应淋巴细胞分泌,目的是杀死病毒感染的细胞。虽然颗粒酶B有效诱导caspase依赖性细胞凋亡的能力早已被认识到,但直到最近才发现人和小鼠颗粒酶B激活重叠但不同的凋亡途径。为了研究这一现象的可能的进化基础,我们对来自多种近缘实验室菌株和野生小鼠的小鼠Gzmb基因的外显子和侧翼内含子序列进行了测序。12/13个自交系的序列编码相同的蛋白质,除了DBA/2,其序列在两个氨基酸上不同。与实验室菌株相比,54只野生小鼠和28只野生自交系小鼠的Gzmb基因存在广泛的多态性,导致预测蛋白存在2-18个氨基酸差异,差异率高达7.3%。这些氨基酸的许多变异都在大鼠和/或人颗粒酶B中发现。自交系实验室菌株的颗粒酶B等位型仅在地理上分散的三个野生小鼠氏族中的一个中被鉴定出来,而在所有28个野生自交系中都没有发现。实验小鼠的近亲castaneus的Gzmb基因与实验菌株相比编码了6个氨基酸差异,这些差异也都在野生小鼠颗粒酶B分子的相应位置上发现。与蛋白酶不同,扩展颗粒酶B在Bid中的识别和切割位点是一个关键的促凋亡底物,是不变的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Tissue antigens
Tissue antigens 医学-病理学
自引率
0.00%
发文量
0
审稿时长
6 months
期刊最新文献
Identification of a novel HLA-DRB1*14 allele, HLA-DRB1*14:143, by sequence-based typing. Identification of the novel HLA-A allele, HLA-A*24:96, in a Chinese individual. CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis. A HLA-A null allele (A*24:132N) with a stop codon in exon 3 generated by a point mutation. Detection of complement-fixing and non-fixing antibodies specific for endothelial precursor cells and lymphocytes using flow cytometry.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1