Genetic disruption of Ano5 in mice does not recapitulate human ANO5-deficient muscular dystrophy.
Genetic disruption of Ano5 in mice does not recapitulate human ANO5-deficient muscular dystrophy.
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DOI：
10.1186/s13395-015-0069-z
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发表时间：
2015
期刊：
影响因子：
4.9
通讯作者：
Han R
中科院分区：
文献类型：
--
作者：
Xu J;El Refaey M;Xu L;Zhao L;Gao Y;Floyd K;Karaze T;Janssen PM;Han R
Anoctamin 5（ANO 5）是保守基因家族（TMEM 16）的成员，其编码的蛋白被预测具有八个跨膜结构域和推定的Ca 2+激活的氯离子通道（CaCC）活性。最近报道，该基因的突变导致肢带型肌营养不良2L型（LGMD 2L）、Miyoshi肌病3型（MMD 3）或颌骨干发育不良1型（GDD 1）的发展。目前，缺乏动物模型来研究Ano 5的生理功能和疾病病理学。在这里，我们报告了第一代Ano 5基因敲除（KO）小鼠的产生和表征。我们的数据表明，KO小鼠从出生到18个月大，在静息条件下没有明显的骨骼肌或心肌病理学。野生型（WT）和KO小鼠之间重复离心收缩后的力产生或力缺陷无显著差异。尽管KO和WT小鼠在每天腹腔注射异丙肾上腺素（ISO，100 mg/kg）治疗2周后心脏肥大的发展相似，但在功能上无法辨别。然而，微阵列分析确定了参与脂质代谢的基因，并且KO骨骼肌中的补体途径发生了改变。综上所述，这些数据提供了证据表明，C57 BL/6 J小鼠中Ano 5的基因消融不会引起骨骼肌和心肌的明显病理学，但Ano 5缺乏可能导致脂质代谢和炎症信号转导的改变。本文的在线版本（doi：10.1186/s13395-015-0069-z）包含补充材料，可供授权用户使用。
Anoctamin 5 (ANO5) is a member of a conserved gene family (TMEM16), which codes for proteins predicted to have eight transmembrane domains and putative Ca2+-activated chloride channel (CaCC) activity. It was recently reported that mutations in this gene result in the development of limb girdle muscular dystrophy type 2L (LGMD2L), Miyoshi myopathy type 3 (MMD3), or gnathodiaphyseal dysplasia 1 (GDD1). Currently, there is a lack of animal models for the study of the physiological function of Ano5 and the disease pathology in its absence. Here, we report the generation and characterization of the first Ano5-knockout (KO) mice. Our data demonstrate that the KO mice did not present overt skeletal or cardiac muscle pathology at rest conditions from birth up to 18 months of age. There were no significant differences in force production or force deficit following repeated eccentric contractions between wild type (WT) and KO mice. Although cardiac hypertrophy developed similarly in both KO and WT mice after daily isoproterenol (ISO, 100 mg/kg) treatment via intraperitoneal injection for 2 weeks, they were functionally indiscernible. However, microarray analysis identified the genes involved in lipid metabolism, and complement pathways were altered in the KO skeletal muscle. Taken together, these data provide the evidence to show that genetic ablation of Ano5 in C57BL/6J mice does not cause overt pathology in skeletal and cardiac muscles, but Ano5 deficiency may lead to altered lipid metabolism and inflammation signaling. The online version of this article (doi:10.1186/s13395-015-0069-z) contains supplementary material, which is available to authorized users.