Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency.
Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency.
复制标题
拳师犬的致心律失常性右心室心肌病与 calstabin2 缺乏有关。
DOI：
10.1016/j.jvc.2008.04.003
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Marks,AndrewR
中科院分区：
文献类型：
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作者：
Oyama,MarkA;Reiken,Steve;Lehnart,StephanE;Chittur,SridarV;Meurs,KathrynM;Stern,Joshua;Marks,AndrewR
目的：探讨心肌病性右室心肌病（ARVC）中钙蛋白2（calstabin 2）缺乏的存在及其影响。方法：对13只ARVC的Boxer犬进行组织病理学、寡核苷酸芯片、PCR、免疫电泳、ryanodine通道免疫沉淀和单通道记录，以及calstabin 2 DNA测序。与健康对照犬相比，心肌钙蛋白2 mRNA和蛋白显著降低（钙蛋白2蛋白标准化为四聚体心脏兰尼碱受体（RyR 2）复合物：受累，0.51±0.04;对照，3.81±0.22; P<0.0001）。Calstabin 2缺乏症与单RyR 2通道开放概率显著增加相关，表明细胞内Ca 2+泄漏。结论Calstabin 2基因缺失可能是Boxer犬ARVC中Ca 2+外漏诱发室性心律失常和心脏病的潜在机制。
OBJECTIVETo examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC).ANIMALSThirteen Boxer dogs with ARVC.MATERIALS AND METHODSTissue samples were collected for histopathology, oligonucleotide microarray, PCR, immunoelectrophoresis, ryanodine channel immunoprecipitation and single-channel recordings, and calstabin2 DNA sequencing.RESULTSIn cardiomyopathic Boxer dogs, myocardial calstabin2 mRNA and protein were significantly decreased as compared to healthy control dogs (calstabin2 protein normalized to tetrameric cardiac ryanodine receptor (RyR2) complex: affected, 0.51±0.04; control, 3.81±0.22; P<0.0001). Calstabin2 deficiency in diseased dog hearts was associated with a significantly increased open probability of single RyR2 channels indicating intracellular Ca2+leak. PCR-based sequencing of the promoter, exonic and splice site regions of the canine calstabin2 gene did not identify any causative mutations.CONCLUSIONSCalstabin2 deficiency is a potential mechanism of Ca2+leak-induced ventricular arrhythmias and heart disease in Boxer dogs with ARVC.