Identification of collagen-induced arthritis loci in aged multiparous female mice
Identification of collagen-induced arthritis loci in aged multiparous female mice
复制标题
DOI：
10.1186/ar1901
复制
发表时间：
2006-01-01
影响因子：
4.9
通讯作者：
Mattsson, Ragnar
中科院分区：
文献类型：
--
作者：
Liljander, Maria;Sallstrom, Mary-Ann;Mattsson, Ragnar
胶原诱导的小鼠关节炎是最常用的自身免疫性实验模型之一，与类风湿性关节炎有许多相似之处。由于胶原诱导的关节炎是一种复杂的多基因疾病，因此需要鉴定几个主要的疾病控制基因。由于类风湿性关节炎特别影响老年女性，我们在本研究中通过研究NFR/N和B10.Q（H-2 q单倍型）之间的杂交老年雌性小鼠，确定了胶原诱导关节炎的新的关键遗传区域。本研究中的小鼠具有不同的生殖史，这对疾病的发作、发病率或严重程度没有显著影响。共200只雌性小鼠用于125个微卫星标记的全基因组筛选。我们发现了一个新的显着的数量性状基因座影响关节炎的发病率，严重程度和发病日的11号染色体（表示Cia 40），共定位与控制妊娠失败的基因座。此外，在1号染色体上发现了一个与发病率、严重程度和发病日期相关的具有提示意义的数量性状位点。最后，在13号染色体上鉴定了与II型胶原抗体滴度相关的显著数量性状位点。这项研究表明，几个基因位点控制关节炎的老年经产女性，这些位点中至少有一个与妊娠失败。
Collagen-induced arthritis in mice is one of the most commonly used autoimmune experimental models, with many similarities to rheumatoid arthritis. Since collagen-induced arthritis is a complex polygenic disease there is a need for identification of several major disease-controlling genes. Because rheumatoid arthritis particularly affects aged women, we have in the present study identified new genetic regions critical for collagen-induced arthritis by studying aged female mice of a cross between NFR/N and B10.Q (H-2q haplotype). The mice in the present study had different reproductive histories, which did not significantly affect the onset, incidence or severity of the disease. A total of 200 female mice were used in a total genomewide screening with 125 microsatellite markers. We found one new significant quantitative trait locus affecting the arthritis incidence, severity and day of onset on chromosome 11 ( denoted Cia40), which colocalizes with a locus controlling pregnancy failure. Furthermore, a quantitative trait locus of suggestive significance associated with the incidence, severity and day of onset was identified on chromosome 1. Finally, a suggestively significant quantitative trait locus associated with collagen type II antibody titers was identified on chromosome 13. This study indicates that several gene loci control arthritis in aged multiparous females, and that at least one of these loci coincides with pregnancy failure.