2024-03-28T17:10:35Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00026362
2023-01-16T04:16:05Z
499:500:501
Congenic mapping and candidate gene analysis for streptozotocin-induced diabetes susceptibility locus on mouse chromosome 11
Maegawa, Tomoki
Miyasaka, Yuki
Kobayashi, Misato
Babaya, Naru
Ikegami, Hiroshi
Horio, Fumihiko
Takahashi, Masahide
Ohno, Tamio
open access
“This is a post-peer-review, pre-copyedit version of an article published in [Mammalian Genome]. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00335-018-9742-y”.
A/J mice
congenic mapping
consomic strain
N-methylpurine DNA glycosylase gene
streptozotocin-induced diabetes susceptibility locus
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-11SM consomic strain and a set of chromosome 11 (Chr. 11) congenic strains developed from A/J-11SM to identify a candidate STZ-induced diabetes susceptibility gene. The A/J strain exhibited significantly higher susceptibility to STZ-induced diabetes than the A/J-11SM strain, confirming the existence of a susceptibility locus on Chr. 11. We named this locus Stzds1 (STZ-induced diabetes susceptibility 1). Congenic mapping using the Chr. 11 congenic strains indicated that the Stzds1 locus was located between D11Mit163 (27.72 Mb) and D11Mit51 (36.39 Mb). The Mpg gene, 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 the Stzds1 region. 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 the Mpg gene 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.
ファイル公開:2019/04/01
Springer
2018-04
eng
journal article
AM
http://hdl.handle.net/2237/00028565
https://nagoya.repo.nii.ac.jp/records/26362
https://doi.org/10.1007/s00335-018-9742-y
0938-8990
1432-1777
Mammalian Genome
29
3-4
273
280
https://nagoya.repo.nii.ac.jp/record/26362/files/Ohno_T_Stzds1.pdf
application/pdf
383.1 kB
2019-04-01