Necrotizing meningoencephalitis of Pug Dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis
Necrotizing meningoencephalitis of Pug Dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis
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DOI：
10.1111/j.1399-0039.2010.01484.x
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发表时间：
2010-08-01
期刊：
影响因子：
--
通讯作者：
Neff, M. W.
中科院分区：
文献类型：
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作者：
Greer, K. A.;Wong, A. K.;Neff, M. W.
坏死性脑膜脑炎（NME）是巴哥犬的一种疾病，根据种群研究，它似乎具有免疫病因学和高遗传性。目前的研究是为了确定这种疾病的遗传基础。单串联重复序列（STR）标记的全基因组关联扫描显示，CFA12上狗白细胞抗原（DLA）复合物附近存在一个强关联。CFA12上27个STR标记的精细定位进一步缩小了与含有DLA-DRB1、-DQA1和-DQB1基因的区域的关联。测序证实，受影响的狗更有可能在每个位点上的特定等位基因是纯合的，这些等位基因是相连的，形成一个单一的高风险单倍型。巴哥犬NME的强DLA II级关联类似于人类多发性硬化症（MS）。与多发性硬化症一样，NME似乎具有自身免疫基础，涉及遗传和非遗传因素，发病率相对较低，女性比男性更常见，并与血管取向的非化脓性炎症有关。然而，巴哥犬的NME在病程中比典型的人类MS更具侵袭性，似乎发病相对较早，并且以坏死而非脱髓鞘为主要病理特征。因此，巴哥犬脑炎（PDE）与不常见的ms急性变异形式具有相同的临床特征。因此，巴哥犬的NME可能代表了人类中枢神经系统某些特发性炎症性疾病的自然发生的犬模型。
Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.