Familial hypertrophic cardiomyopathy in Maine coon cats - An animal model of human disease
Familial hypertrophic cardiomyopathy in Maine coon cats - An animal model of human disease
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DOI：
10.1161/01.cir.99.24.3172
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发表时间：
1999-06-22
期刊：
影响因子：
37.8
通讯作者：
Towbin, JA
中科院分区：
文献类型：
--
作者：
Kittleson, MD;Meurs, KM;Towbin, JA
背景-缺乏家族性肥厚型心肌病（FHCM）的自然发生的动物模型，我们鉴定了一个患有HCM的缅因州浣熊家族，并建立了一个群体来确定遗传模式、表型表达和疾病的自然史。受影响和未受影响的猫进行繁殖，以确定遗传模式。超声心动图用于识别受影响的后代并确定表型表达。连续重复超声心动图以确定疾病的自然史。从繁殖受影响的猫到未受影响的猫的22个后代中，12个（55%）受到影响。当患病猫与患病猫交配时，9只猫中有4只（45%）受影响，2只（22%）未受影响，3只（33%）死胎。研究结果与常染色体显性遗传模式一致，100%染色体畸变率，而染色体畸变率代表在子宫内死亡的致死性纯合子。受影响的猫通常在6个月龄之前没有HCM的表型证据，在青春期发展HCM，并在年轻成年期发展严重的HCM，乳头肌肥大导致中腔阻塞和二尖瓣收缩期前向运动是HCM最一致的表现。猫突然死亡（n = 5）或心力衰竭（n = 3）。心肌组织学显示心肌纤维紊乱，壁内冠状动脉粥样硬化，间质纤维化，结论HCM在这个家庭的缅因州浣熊密切类似于人类形式的FHCM，并应证明一个有价值的工具，用于研究的总，细胞和分子病理生理学的疾病。
Background-A naturally occurring animal model of familial hypertrophic cardiomyopathy (FHCM) is lacking, We identified a family of Maine coon cats with HCM and developed a colony to determine mode of inheritance, phenotypic expression, and natural history of the disease.Methods and results-a proband was identified, and related cats were bred to produce a colony. Affected and unaffected cats were bred to determine the mode of inheritance. Echocardiography was used to identify affected offspring and determine phenotypic expression, Echocardiograms were repeated serially to determine the natural history of the disease. Of 22 offspring from breeding affected to unaffected cats, 12 (55%) were affected. When affected cats were bred to affected cats, 4 (45%) of the 9 were affected, 2 (22%) unaffected, and 3 (33%) stillborn. Findings were consistent with an autosomal dominant mode of inheritance with 100% penetrance, with the stillborns representing lethal homozygotes that died in utero. Affected cats usually did not have phenotypic evidence of HCM before 6 months of age, developed HCM during adolescence, and developed severe HCM during young adulthood, Papillary muscle hypertrophy that produced midcavitary obstruction and systolic anterior motion of the mitral valve was the most consistent manifestation of HCM. Cats died suddenly (n = 5) or of heart failure (n = 3). Histopathology of the myocardium revealed myocardial fiber disarray, intramural coronary arteriosclerosis, and interstitial fibrosis,Conclusions-HCM in this family of Maine coon cats closely resembles the human form of FHCM and should prove a valuable tool for studying the gross, cellular, and molecular pathophysiology of the disease.