Wagner J L, Burnett R C, Storb R
Fred Hutchinson Cancer Research Center, Program in Transplantation Biology, Seattle, WA 98109-1024, USA.
J Hered. 1999 Jan-Feb;90(1):35-8. doi: 10.1093/jhered/90.1.35.
The dog is a valuable model for studying several human diseases as well as one of the most important models for organ transplantation. Important to understanding the pathophysiology or development of some of these diseases is an understanding of the canine major histocompatibility complex (MHC) or dog leukocyte antigen (DLA). Initial characterization of the DLA involved primarily cellular, serological, and biochemical analyses. Later a molecular analysis of the DLA region was begun. There are at least four complete class I genes: DLA-88, DLA-12, DLA-64, and DLA-79. DLA-88 is highly polymorphic, with more than 40 alleles obtained from an examination of 50 mixed breed dogs. The other class I loci are less polymorphic, with fewer than 12 alleles each. In the class II region there is one complete DRB gene called DLA-DRB1 with at least 24 alleles and one full-length DQB gene, DLA-DQB1, with 20 alleles characterized to date. DLA-DQA is less polymorphic with nine alleles and DLA-DRA appears monomorphic. Two highly polymorphic canine microsatellite markers, one located in the class I region and one located in the class II region, can be used to identify DLA-matched and -mismatched dogs within families for organ transplantation experiments. Future projects include mapping the DLA region by pulsed-field gel electrophoresis and using a recently constructed canine bacterial artificial chromosome (BAC) library to search for new genes within the DLA. The dog has been a useful model for understanding several human diseases such as gluten-sensitive enteropathy (Hall and Batt 1990), rheumatoid arthritis (Halliwell et al. 1972), narcolepsy (Tafti et al. 1996), and systemic lupus erythematosus (Lewis and Schwartz 1971, Teichner et al. 1990), as well as an important model for solid organ and hematopoietic stem cell transplantation (Storb and Deeg 1985). Much of the impetus behind efforts to characterize the canine MHC comes from its importance in transplantation. In spite of the dog's importance in studying human disease and in immunology, molecular analysis of the DLA has lagged behind that of the mouse and human as well as several agricultural animals.
狗是研究多种人类疾病的重要模型，也是器官移植最重要的模型之一。理解这些疾病中的一些疾病的病理生理学或发展过程的关键在于了解犬类主要组织相容性复合体（MHC）或犬白细胞抗原（DLA）。对DLA的初步表征主要涉及细胞、血清学和生化分析。后来开始了对DLA区域的分子分析。至少有四个完整的I类基因：DLA - 88、DLA - 12、DLA - 64和DLA - 79。DLA - 88具有高度多态性，通过对50只混种犬的检测获得了40多个等位基因。其他I类基因座的多态性较低，每个基因座的等位基因少于12个。在II类区域，有一个完整的DRB基因称为DLA - DRB1，至少有24个等位基因，还有一个全长的DQB基因DLA - DQB1，迄今为止已鉴定出20个等位基因。DLA - DQA的多态性较低，有9个等位基因，而DLA - DRA似乎是单态的。两个高度多态的犬类微卫星标记，一个位于I类区域，一个位于II类区域，可用于在家庭中识别DLA匹配和不匹配的狗，用于器官移植实验。未来的项目包括通过脉冲场凝胶电泳对DLA区域进行图谱绘制，并使用最近构建的犬类细菌人工染色体（BAC）文库在DLA内寻找新基因。狗一直是理解多种人类疾病的有用模型，如麸质敏感性肠病（Hall和Batt，1990年）、类风湿性关节炎（Halliwell等人，1972年）、发作性睡病（Tafti等人，1996年）和系统性红斑狼疮（Lewis和Schwartz，1971年；Teichner等人，1990年），也是实体器官和造血干细胞移植的重要模型（Storb和Deeg，1985年）。对犬类MHC进行表征的许多努力背后的主要推动力来自其在移植中的重要性。尽管狗在研究人类疾病和免疫学方面很重要，但对DLA的分子分析落后于小鼠、人类以及几种家畜。
