Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA.
Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA.
复制标题
1号染色体上的基因组位点调节IL-1RA缺陷小鼠对自发性关节炎的易感性。
DOI：
10.1186/s12865-014-0057-9
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发表时间：
2014-12-09
期刊：
影响因子：
3
通讯作者：
Gu W
中科院分区：
文献类型：
--
作者：
Deng N;Jiao Y;Cao Y;Liu X;Ma Y;Hasty KA;Brand DD;Stuart JM;Gu W
BackgroundTo understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1−/−mice that are resistant to spontaneous arthritis into BALB/c−/−mice which are susceptible. We were able to establish two congenic strains which exhibited a delayed onset and reduced severity of disease. In this study, we asked a different set of questions. How will the QTL region from BALB/c−/−interact with the rest of the genome in the DBA/1−/−background? Will the DBA/1−/−mice become susceptible to spontaneous arthritis if the QTL genomic region on chromosome 1 was replaced with the genomic fragment of the same region from BALB/c−/−? We conducted the congenic breeding with the similar procedure as that of congenic strains with BALB/c−/−background.ResultInstead of BALB/c−/−, DBA/1−/−was used as the recurrent parent while BALB/c−/−was used as the donor parent. By the 6thgeneration we determined that all of the chromosomes in the progeny were of DBA/1−/−origin with the exception of the QTL portion of chromosome 1 which is heterozygous of BALB/c−/−and DBA/1−/−origin. We then intercrossed selected mice to produce homozygous strains containing the homozygous genomic region of BALB/c−/−on chromosome 1, while the rest of genome are homozygous DBA/1−/−. This strain was observed for the development of spontaneous arthritis. Up to 9 weeks of age, both congenic strain and DBA/1−/−did not develop arthritis. However, after 9 weeks, the congenic strain started to exhibit signs of arthritis, while the DBA/1−/−remained free from disease.ConclusionThe result indicates a strong influence of genetic factor(s) on the QTL of chromosome 1 on the susceptibility to spontaneous arthritis. Identification of genetic factors within this QTL region in the future will significantly enhance our understanding of molecular mechanism of spontaneous arthritis.
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影响因子：
15.9
作者：
Abdollahi-Roodsaz, Shahla;Joosten, Leo A. B.;Van den Berg, Wim B.
通讯作者：
Van den Berg, Wim B.
影响因子：
15.9
作者：
Horai, R;Nakajima, A;Iwakura, Y
通讯作者：
Iwakura, Y
影响因子：
--
作者：
Zhou, F;He, XW;Stuart, JM
通讯作者：
Stuart, JM
同源小鼠为调节 IL-1RA 缺乏引起的自发性关节炎的基因位点提供了证据
影响因子：
3.7
作者：
Cao Y;Liu X;Deng N;Jiao Y;Ma Y;Hasty KA;Stuart JM;Gu W
通讯作者：
Gu W
影响因子：
5.4
作者：
Stephens, Geoffrey L.;Wang, Qun;Fung, Michael
通讯作者：
Fung, Michael