Congenic mice provide evidence for a genetic locus that modulates spontaneous arthritis caused by deficiency of IL-1RA.
Congenic mice provide evidence for a genetic locus that modulates spontaneous arthritis caused by deficiency of IL-1RA.
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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
DOI：
10.1371/journal.pone.0068158
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gu W
中科院分区：
文献类型：
--
作者：
Cao Y;Liu X;Deng N;Jiao Y;Ma Y;Hasty KA;Stuart JM;Gu W
为了了解遗传因素在IL-1受体拮抗剂蛋白（IL_1RA）缺乏小鼠自发性关节炎发展中的作用，我们已经确定了一个包含该疾病主要数量性状位点（QTL）的基因组区域。QTL位于1号染色体上，似乎是调节关节炎最强的遗传区域。为了确认QTL的重要性并鉴定其中潜在的候选基因，我们进行了快速遗传育种，将具有自发性关节炎抗性的DBA/1小鼠的QTL区域转移到易感的BALB/c−/−小鼠中。利用每条染色体上的遗传标记帮助选择每一代回交BALB/c−/−的后代。到第6代，我们确定除了1号染色体部分外，后代的所有染色体都是BALB/c起源。在这一阶段，我们将选择的小鼠进行交叉杂交，产生除1号染色体上的QTL区域来自DBA/1外具有BALB/c−/−基因组背景的纯合子菌株。我们能够建立两个具有重叠DBA/1 DNA片段的同源菌株。这些菌株被观察为自发性关节炎的发展。这两种基因菌株对自发性关节炎都有相对的抵抗力，并且发病延迟，疾病严重程度降低。调控这个主要QTL的基因/s似乎位于两个菌株共享的QTL区域。共同转移区位于1号染色体上的D1Mit110和D1Mit209之间。我们评估了该区域的候选基因，并确定了有限数量的候选基因。确认候选人的身份和确切角色将需要进一步研究。
To understand the role of genetic factors involved in the development of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we have identified a genomic region containing a major quantitative trait locus (QTL) for this disease. The QTL is on chromosome 1 and appears to be the strongest genetic region regulating arthritis. To confirm the importance of the QTL and to identify potential candidate genes within it, we conducted speed congenic breeding to transfer the QTL region from DBA/1 mice that are resistant to spontaneous arthritis into BALB/c−/− which are susceptible. Genetic markers along every chromosome were used to assist in the selection of progeny in each generation to backcross to BALB/c−/−. By the 6th generation we determined that all of the chromosomes in the progeny were of BALB/c origin with the exception of portions of chromosome 1. At this stage we intercrossed selected mice to produce homozygous strains containing the genomic background of BALB/c−/− except for the QTL region on chromosome 1, which was from DBA/1. We were able to establish two congenic strains with overlapping DBA/1 DNA segments. These strains were observed for the development of spontaneous arthritis. Both congenic strains were relatively resistant to spontaneous arthritis and had delayed onset and reduced severity of disease. The gene/s that regulates this major QTL would appear to be located in the region of the QTL that is shared by both strains. The common transferred region is between D1Mit110 and D1Mit209 on chromosome 1. We evaluated this region for candidate genes and have identified a limited number of candidates. Confirmation of the identity and precise role of the candidates will require additional study.
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DOI：
10.1084/jem.191.2.313
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horai R;Saijo S;Tanioka H;Nakae S;Sudo K;Okahara A;Ikuse T;Asano M;Iwakura Y
通讯作者：
Iwakura Y
影响因子：
2.5
作者：
Armstrong, NJ;Brodnicki, TC;Speed, TP
通讯作者：
Speed, TP
DOI：
10.1056/nejmoa0807865
发表时间：
2009-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aksentijevich I;Masters SL;Ferguson PJ;Dancey P;Frenkel J;van Royen-Kerkhoff A;Laxer R;Tedgård U;Cowen EW;Pham TH;Booty M;Estes JD;Sandler NG;Plass N;Stone DL;Turner ML;Hill S;Butman JA;Schneider R;Babyn P;El-Shanti HI;Pope E;Barron K;Bing X;Laurence A;Lee CC;Chapelle D;Clarke GI;Ohson K;Nicholson M;Gadina M;Yang B;Korman BD;Gregersen PK;van Hagen PM;Hak AE;Huizing M;Rahman P;Douek DC;Remmers EF;Kastner DL;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
DOI：
10.4049/jimmunol.181.2.859
发表时间：
2008-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Xiong Q;Jiao Y;Hasty KA;Stuart JM;Postlethwaite A;Kang AH;Gu W
通讯作者：
Gu W
影响因子：
15.9
作者：
Horai, R;Nakajima, A;Iwakura, Y
通讯作者：
Iwakura, Y