GENES ON THE X-CHROMOSOME AFFECT DEVELOPMENT OF COLLAGEN-INDUCED ARTHRITIS IN MICE
GENES ON THE X-CHROMOSOME AFFECT DEVELOPMENT OF COLLAGEN-INDUCED ARTHRITIS IN MICE
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DOI：
10.1111/j.1365-2249.1993.tb08218.x
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发表时间：
1993-12-01
影响因子：
4.6
通讯作者：
HOLMDAHL, R
中科院分区：
文献类型：
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作者：
JANSSON, L;HOLMDAHL, R
小鼠对胶原诱导关节炎（CIA）的易感性与MHC中的II类基因（a (q)）有关，但也与MHC外的未知基因有关。这里研究的是基因对X染色体的影响以及X连锁免疫缺陷（xid）突变的作用。对A(q)进行杂合或纯合的互易雄性F-1杂交种，其对CIA的易感性受遗传影响。在B10之间进行了交叉。G, B10。Q dba /1 swr / j c3h。Q和CBA/Ca，所有F-1小鼠均被阉割，以避免性激素调节易感性。在互惠的F-1男性中可以看到关节炎发病和严重程度的不同时间。一个例外是来自SWR/J和DBA/1杂交的F-1雄性后代，它们仅在疾病过程后期的疾病严重程度上存在差异。雌性F-1杂交与雄性F-1杂交没有表现出相同的CIA敏感性差异模式。为了排除Y染色体可能的影响，将互惠杂交的F-1雄性与亲本菌株回交，产生X染色体相等但Y染色体不同的后代。在这些人中没有观察到关节炎发展的差异。接下来研究了xid突变的影响。将CBA/N小鼠的xid位点选育到CIA高度敏感的DBA/1菌株中。由此产生的基因DBA/1-xid菌株对CIA的诱导具有抗性，并且对II型胶原没有产生抗体反应。我们得出结论，X染色体上的多态性基因调节对CIA的易感性，从携带xid突变的小鼠的实验结果证实，这种免疫调节基因存在于性染色体上。
Susceptibility to collagen-induced arthritis (CIA) in mice is associated with a class II gene in MHC (A(q)) but also with unknown genes outside MHC. Investigated here is the influence of genes on the X chromosome as well as the role of the X-linked immunodeficiency (xid) mutation. Reciprocal male F-1 hybrids, bred to be heterozygous or homozygous for A(q), showed a genetic influence in their susceptibility to develop CIA. Crosses were made between B10.G, B10.Q, DBA/1, SWR/J, C3H.Q and CBA/Ca, and all F-1 mice were castrated to avoid sex hormone modulation of the susceptibility. A differential timing of arthritis onset and severity were seen in the reciprocal F-1 males. An exception was the reciprocal F-1 male offspring from SWR/J and DBA/1 crosses which differed only in disease severity late in the course of the disease. The female F-1 crosses did not show the same pattern of differential susceptibility to CIA as the F-1 males. To exclude the possible influence of the Y chromosome, F-1 males of reciprocal crosses were back-crossed to the parental strains creating offspring with equal X chromosomes but divergent Y chromosomes. No difference in development of arthritis was observed in these. The influence of the xid mutation was investigated next. The xid loci from the CBA/N mouse was bred into DBA/1 strain which is highly susceptible to CIA. The resulting congenic DBA/1-xid strain was resistant to induction of CIA and did not develop an antibody response to type II collagen. We conclude that polymorphic genes on the X chromosome modulate susceptibility to CIA, The results from the experiments with mice carrying xid mutations confirm that such immune modulating genes exist on the sex chromosomes.