CANINE MODELS OF FAMILIAL DILATED CARDIOMYOPATHY

扩张型心肌病（DCM）是一种原发性心肌疾病 以收缩功能障碍和心室扩张为特征;它 在许多物种中自然发生。(1-3)约20%的人DCM 似乎是家族起源，和特点可能是遗传在一个 常染色体（显性或隐性）、X连锁或线粒体 格局（4，5）也存在家族性DCM的犬模型。大于50% 被诊断患有扩张型心肌病的狗是杜宾犬， 与人类家族性扩张型心肌病相似(6-8)金毛猎犬也是 已知患有家族性DCM，有时患有与 与杜氏肌营养不良症（DMD）相似的肌营养不良症， 人类（9-12）除了DCM之外，还显示肌营养不良蛋白异常。 在某些情况下。（13-15）我们认为，一个自然的动物模型， 扩张型心肌病可以提供机会，研究至少一个原因扩张型心肌病在 为人类疾病提供候选基因模型。 患有DCM的杜宾犬和金毛猎犬的谱系已经被 收集;受影响和未受影响个体的表型 表征了还从受影响者和 未受影响的家庭成员发展成淋巴母细胞样细胞系作为一种 DNA的来源，并用于DNA分离。那些狗屈服了 将进行尸检;心脏和骨骼肌样本已被 获得（可能时新鲜冷冻，或福尔马林固定）。杜宾 从个体中分离的pinscher和金毛寻回犬DNA（血液， 组织）将进行连锁分析以绘制染色体基因座 负责DCM和该地区将被克隆，以隔离和识别 在进行突变分析之前确定相关基因。此外，样品 将通过多重PCR和其他方法分析肌营养不良蛋白缺失 突变。(16这项研究最终将提供一种天然动物， 在分子水平上研究家族性DCM的模型， 提供候选基因用于用这种形式的 心肌病，以及潜在地提高DCM的知识， DMD和X连锁DCM，由于肌营养不良蛋白异常引起的人类疾病。（十八）

Dilated cardiomyopathy(DCM) is a primary heart muscle disease characterized by systolic dysfunction and ventricular dilatation; it occurs naturally in many species.(1-3) Approximately 20% of human DCM appears to be of familial origin, and the trait may be inherited in an autosomal (dominant or recessive), X-linked, or mitochondrial pattern.(4,5) Canine models of familial DCM also exists. Greater than 50% of dogs diagnosed as having DCM are Doberman pinschers and they have close similarities to familial DCM in humans. (6-8) Golden retrievers are also known to have familial DCM and sometimes have DCM associated with a muscular dystrophy similar to Duchenne muscular dystrophy (DMD) in humans.(9-12) In addition to DCM, dystrophin abnormalities have been shown in some cases. (13-15) We believe that a natural animal model of familial DCM could provide opportunities to study at least one cause of DCM at the molecular level and provide a candidate gene model for human disease. Pedigrees from Doberman pinschers and golden retrievers with DCM have been collected; the phenotypes of affected and unaffected individuals were characterized. Blood samples have also been obtained from affected and unaffected family members to develop lymphoblastoid cell lines as an immortalized.source of DNA, and for DNA isolation. Those dogs succumbing to DCM will be autopsied; cardiac and skeletal muscle samples have been obtained (fresh frozen when possible, or formalin-fixed). Doberman pinscher and golden retriever DNA isolated from individuals (blood, tissue) will be subjected to linkage analysis to map the chromosomal locus responsible for DCM and the region will be cloned to isolate and identify the responsible gene prior to performing mutation analysis. Also, samples will be analyzed for dystrophin deletions by multiplex PCR and other mutations.(16,17) This study will ultimately provide a natural animal model in which to study familial DCM at a molecular level and potentially provide a candidate gene(s) for evaluation in humans with this form of cardiomyopathy, as well as potentially improving the knowledge of DCM in DMD and X-linked DCM, human diseases due to dystrophin abnormalities.(18)