GENETIC, HORMONAL AND BEHAVIORAL INFLUENCE ON SPONTANEOUSLY DEVELOPING ARTHRITIS IN NORMAL MICE
GENETIC, HORMONAL AND BEHAVIORAL INFLUENCE ON SPONTANEOUSLY DEVELOPING ARTHRITIS IN NORMAL MICE
复制标题
DOI：
10.1111/j.1365-2249.1992.tb06473.x
复制
发表时间：
1992-06-01
影响因子：
4.6
通讯作者：
JONSSON, R
中科院分区：
文献类型：
--
作者：
HOLMDAHL, R;JANSSON, L;JONSSON, R
DBA/1 雄性小鼠在 4 个月大时自发出现关节炎。 受影响的关节显示出富含细胞的血管翳形成，没有 T 细胞浸润，并且仅有有限的 MHC II 类表达。 不同来源的无特定病原体的 DBA/1 小鼠患上了相同的疾病。 对具有不同遗传背景的近交小鼠品系和 F1 杂种的分析表明，该疾病在遗传上依赖于 DBA/1 隐性基因。 然而，DBA/1 和 BXSB 之间的 F1 杂种自发地出现关节炎，且比 DBA/1 小鼠发病更早，这表明 BXSB 自身免疫基因背景对关节炎的发生既具有许可作用，又具有促进作用。 通过对 DBA/1 男性进行去势和睾酮治疗，研究了男性对疾病易感性的完全优势。 去势后没有出现关节炎，并且通过睾酮治疗恢复了疾病易感性。 只有当两只以上的雄性被关在笼子里时才会出现关节炎，这表明攻击性行为的影响。 因此，关节炎的自发发展依赖于激素和行为介导的作用，并且不同于类风湿性关节炎的实验模型，例如II型胶原诱导的关节炎和降植烷诱导的关节炎。 我们得出的结论是，正常 DBA/1 菌株中自发发生的关节炎作为骨关节炎的疾病模型可能比类风湿性关节炎更有用。
DBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus formation without T cell infiltration and only limited MHC class II expression. Specific pathogen-free DBA/1 mice from different sources developed the same disease. Analyses of inbred mouse strains with various genetic backgrounds and F1 hybrids revealed that the disease is genetically dependent of DBA/1 recessive genes. However, F1 hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/1 mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing effects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development of arthritis is dependent on hormonal and behavioural mediated effects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristane-induced arthritis. We conclude that the spontaneously developing arthritis in the normal DBA/1 strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis.