Croxford J L, O'Neill J K, Baker D
Department of Clinical Ophthalmology, Institute of Ophthalmology, University College London, UK.
J Neuroimmunol. 1997 Apr;74(1-2):205-11. doi: 10.1016/s0165-5728(96)00219-6.
Experimental allergic encephalomyelitis (EAE) is a chronic inflammatory disease of the central nervous system (CNS), with many similarities to multiple sclerosis (MS). Susceptibility to EAE is under genetic control of both the major histocompatibility complex (MHC) and unknown non-MHC gene products. This study uses a selective cross between EAE-susceptible ABH and low responder BALB/c mice, where disease is dominant and affects female mice significantly more than males. In a genome screen using microsatellite markers, linkage analysis suggests that genes encoded on chromosomes 4, 8, 10, 11, 12 and 17 contribute to the development of EAE (p < 0.05), although none of these putative EAE loci fulfilled the criteria for significant linkage. Interestingly, genotype frequency showed significant deviation from the expected random distribution of alleles on chromosomes 4, 8 and 17, (p < 0.001), with 32% of mice developing disease, exhibiting all 3 alleles (p < 0.001). This may indicate complex interactions amongst gene products in the EAE phenotype. This and other recent studies in different mouse strains underlies that EAE is a complex polygenic trait and may provide clues to the genetic mechanisms involved in autoimmune diseases such as multiple sclerosis.
实验性自身免疫性脑脊髓炎（EAE）是一种中枢神经系统（CNS）的慢性炎症性疾病，与多发性硬化症（MS）有许多相似之处。EAE的易感性受主要组织相容性复合体（MHC）和未知的非MHC基因产物的遗传控制。本研究使用EAE易感的ABH小鼠和低反应性的BALB/c小鼠进行选择性杂交，其中疾病是显性的，对雌性小鼠的影响明显大于雄性小鼠。在使用微卫星标记的基因组筛选中，连锁分析表明，位于4号、8号、10号、11号、12号和17号染色体上编码的基因对EAE的发展有贡献（p < 0.05），尽管这些假定的EAE基因座均未达到显著连锁的标准。有趣的是，基因型频率显示出与4号、8号和17号染色体上等位基因预期随机分布的显著偏差（p < 0.001），32%的小鼠发病，表现出所有3个等位基因（p < 0.001）。这可能表明EAE表型中基因产物之间存在复杂的相互作用。这项研究以及最近在不同小鼠品系中的其他研究表明，EAE是一种复杂的多基因性状，可能为多发性硬化症等自身免疫性疾病的遗传机制提供线索。
