Congenic mapping and candidate gene analysis for streptozotocin-induced diabetes susceptibility locus on mouse chromosome 11
Congenic mapping and candidate gene analysis for streptozotocin-induced diabetes susceptibility locus on mouse chromosome 11
复制标题
小鼠11号染色体上链脲佐菌素诱导的糖尿病易感位点的同源作图及候选基因分析
DOI：
10.1007/s00335-018-9742-y
复制
发表时间：
2018
期刊：
影响因子：
2.5
通讯作者：
Ohno Tamio
中科院分区：
文献类型：
--
作者：
Maegawa Tomoki;Miyasaka Yuki;Kobayashi Misato;Babaya Naru;Ikegami Hiroshi;Horio Fumihiko;Takahashi Masahide;Ohno Tamio
链脲佐菌素（STZ）已被广泛用于诱发啮齿动物糖尿病。已经报道了对STZ敏感性的菌株依赖性变化;然而，负责STZ敏感性的基因尚未被鉴定。在这里，我们利用A/J-11 SM同源株和一组11号染色体（Chr.11）同源株开发的A/J-11 SM，以确定一个候选STZ诱导的糖尿病易感基因。A/J菌株对STZ诱导的糖尿病的易感性显著高于A/J-11 SM菌株，证实了在第11染色体上存在易感性位点。我们将该位点命名为Stzds 1（STZ诱导的糖尿病易感性1）。利用11号染色体同源株进行同源基因定位，结果表明，Stzds 1位点位于D11 Mit 163（27.72 Mb）和D11 Mit 51（36.39 Mb）之间。Mpg基因编码N-甲基嘌呤DNA糖基化酶（MPG），一种普遍存在的DNA修复酶，负责去除DNA中烷基化碱基损伤，位于Stzds 1区域内。STZ作用早期的DNA烷基化与MPG的作用密切相关。对Mpg基因的桑格序列分析显示A/J基因组中有5个多态性位点。一个变异体，p.Ala132Ser，位于啮齿动物物种之间的高度保守区域，并在最小区域保留酶活性的MPG。这可能是由于p.Ala132Ser突变引起的MPG结构改变，增加了STZ对DNA中烷基化碱基损伤的识别和切除。
Streptozotocin (STZ) has been widely used to induce diabetes in rodents. Strain-dependent variation in susceptibility to STZ has been reported; however, the gene(s) responsible for STZ susceptibility has not been identified. Here, we utilized the A/J-11SMconsomic strain and a set of chromosome 11 (Chr. 11) congenic strains developed from A/J-11SMto identify a candidate STZ-induced diabetes susceptibility gene. The A/J strain exhibited significantly higher susceptibility to STZ-induced diabetes than the A/J-11SMstrain, confirming the existence of a susceptibility locus on Chr. 11. We named this locusStzds1(STZ-induced diabetes susceptibility 1). Congenic mapping using the Chr. 11 congenic strains indicated that theStzds1locus was located betweenD11Mit163(27.72 Mb) andD11Mit51(36.39 Mb). TheMpggene, which encodes N-methylpurine DNA glycosylase (MPG), a ubiquitous DNA repair enzyme responsible for the removal of alkylated base lesions in DNA, is located within theStzds1region. There is a close relationship between DNA alkylation at an early stage of STZ action and the function of MPG. A Sanger sequence analysis of theMpggene revealed five polymorphic sites in the A/J genome. One variant, p.Ala132Ser, was located in a highly conserved region among rodent species and in the minimal region for retained enzyme activity of MPG. It is likely that structural alteration of MPG caused by the p.Ala132Ser mutation elicits increased recognition and excision of alkylated base lesions in DNA by STZ.
登录
查看更多内容
影响因子：
3.8
作者：
Burns, Nicole;Gold, Barry
通讯作者：
Gold, Barry
A/J-Chr 11(SM) 小鼠的身体和主要器官重量。
DOI：
--
发表时间：
2009
期刊：
Exp.Anim.
影响因子：
--
作者：
Tanaka;S.;Mizorogi;T.;Nishijima;K.;Kuwahara;S.;Tsujio;M.;Aoyama;H.;Taguchi;C.;Kobayashi;M.;Horio;F. and Ohno;T
通讯作者：
T
人类和大鼠胰岛暴露于一氧化氮、过氧亚硝酸盐和细胞因子后的胰岛素分泌、DNA 损伤和细胞凋亡。
DOI：
--
发表时间：
1998
期刊：
Nitric oxide
影响因子：
--
作者：
V. Hadjivassiliou;M. Green;Michael H.L. Green;R. F. L. James;S. Swift;H. Clayton;Irene C. Green;Irene C. Green
通讯作者：
Irene C. Green
哺乳动物碱基切除修复酶 N-甲基嘌呤-DNA 糖基化酶的结构域
影响因子：
4.8
作者：
R. Roy;Amalendra Kumar;J. Lee;S. Mitra
通讯作者：
S. Mitra
DOI：
10.1073/pnas.96.6.3059
发表时间：
1999-03-16
影响因子：
11.1
作者：
Pieper, AA;Brat, DJ;Snyder, SH
通讯作者：
Snyder, SH