DLA-DQB1 alleles and bone marrow transplantation experiments in narcoleptic dogs.
DLA-DQB1 alleles and bone marrow transplantation experiments in narcoleptic dogs.
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发作性睡病犬的 DLA-DQB1 等位基因和骨髓移植实验。
DOI：
10.1034/j.1399-0039.2000.560304.x
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Mignot,E
中科院分区：
文献类型：
--
作者：
Wagner,JL;Storb,R;Storer,B;Mignot,E
人类嗜睡症是一种已知与HLA-DQB 1 *0602密切相关的神经系统疾病。临床上类似的疾病已被描述在各种狗品种。这种疾病的犬形式在拉布拉多寻回犬和杜宾犬（canarc-1）中遗传为常染色体隐性遗传病，但在其他品种中偶尔发生，最典型的是腊肠犬和贵宾犬。在这项研究中，我们检查了发作性睡病的发生与特定犬白细胞抗原（DLA）-DQB 1等位基因之间是否存在关系。对99只犬和68只对照动物进行了DLA‐ DQB 1 -31发作性睡病分型。最近的研究表明，常染色体隐性遗传性发作性睡病的发生与下丘脑泌素受体2（Hcrtr 2）基因的破坏有关，该基因位于与犬MHC区域（CFA 12）相同的染色体上，但不靠近DLA。在DLA-DQ水平分析了4个Hcrtr 2阳性家族（2个杜宾犬家族、1个拉布拉多寻回犬家族、1个腊肠犬家族）。在Hcrtr 2介导的发作性睡病中，未发现发作性睡病与DLA之间的关系，但观察到松散的遗传连锁（Zmax=2.3，θ= 25%，m =40）。两个DLA相同的受影响（Hcrtr 2-/-）和未受影响（Hcrtr 2 +/-）的兄弟姐妹之间的骨髓移植也进行了研究，发现既不能成功地传播嗜睡症，也不能缓解杜宾犬的症状。接下来在11只散发性（非家族性）发作性睡病犬和相同和不同品种的无关对照动物中研究了DLA-DQB 1。分析了各种DLA-DQB 1等位基因的等位基因和携带者频率。发作性睡病的发生与特异性DLA-DQB 1等位基因之间没有强的正相关或负相关。这些结果不支持DLA-DQ参与犬发作性睡病，无论是散发性还是家族性起源。
Human narcolepsy is a neurological disorder known to be tightly associated with HLA‐DQB1*0602. A clinically similar disorder has been described in various dog breeds. The canine form of the disease is inherited as an autosomal recessive disorder in Labrador retrievers and Doberman pinschers (canarc‐1) but occurs sporadically in other breeds, most typically dachshunds and poodles. In this study, we have examined if there is a relationship between the development of narcolepsy and specific dog leukocyte antigen (DLA)‐DQB1 alleles. Ninety‐nine dogs were typed for DLA‐DQB1–31 with narcolepsy and 68 control animals. Recent studies have linked the development of autosomal recessive canine narcolepsy to a disruption of thehypocretin receptor 2(Hcrtr2) gene on the same chromosome as the canine MHC region (CFA12), but not close to the DLA. FourHcrtr2‐positive families (two Doberman pinscher families, one Labrador retriever family, one dachshund family) were analyzed at the DLA‐DQ level. No relationship was found between narcolepsy and DLA inHcrtr2‐mediated narcolepsy but loose genetic linkage was observed (Zmax=2.3 at θ=25%,m=40). Bone marrow transplantation between two DLA identical affected (Hcrtr2−/−) and unaffected (Hcrtr2+/−) siblings was also performed and found not to be successful neither in transmitting narcolepsy nor in relieving the symptoms in Doberman pinschers. DLA‐DQB1 was next studied in 11 dogs with sporadic (non‐familial) narcolepsy and in unrelated control animals of the same and different breeds. The allelic and carrier frequencies of various DLA‐DQB1 alleles were analyzed. There was no strong positive or negative correlation between the development of narcolepsy and specific DLA‐DQB1 alleles. These results do not support the involvement of DLA‐DQ in canine narcolepsy, whether of sporadic or familial origin.
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