Targeted disruption of the murine Bin1/Amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation
Targeted disruption of the murine Bin1/Amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation
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DOI：
10.1128/mcb.23.12.4295-4306.2003
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发表时间：
2003-06-01
影响因子：
5.3
通讯作者：
Prendergast, GC
中科院分区：
文献类型：
--
作者：
Muller, AJ;Baker, JF;Prendergast, GC
哺乳动物Bin1/Amphiphysin II基因编码一系列可选择剪接的适配器蛋白，这些蛋白表现出明显不同的表达和亚细胞定位谱。BinI蛋白参与多种不同的细胞过程，包括内吞作用、肌动蛋白细胞骨架组织、转录和应激反应。为了深入了解Bin1基因的生理功能，我们在小鼠中通过同源重组破坏了它。Bin1缺失对小鼠胚胎源性成纤维细胞和巨噬细胞的内吞作用和吞噬作用均无明显影响。同样，胚胎成纤维细胞中的肌动蛋白细胞骨架组织、增殖和凋亡都不受Bin1缺失的影响。然而，在体内，Bin1缺失导致围产期死亡。Bin1已被报道影响肌肉细胞分化和t小管的形成。Bin1胚胎骨骼肌未见明显组织学异常，但有严重的室性心肌病。在超微结构上，Bin1胚胎心室心肌细胞的肌原纤维严重紊乱。这些结果确定了Bin1基因在心肌发育中的关键作用。
The mammalian Bin1/Amphiphysin II gene encodes an assortment of alternatively spliced adapter proteins that exhibit markedly divergent expression and subcellular localization profiles. BinI proteins have been implicated in a variety of different cellular processes, including endocytosis, actin cytoskeletal organization, transcription, and stress responses. To gain insight into the physiological functions of the Bin1 gene, we have disrupted it by homologous recombination in the mouse. Bin1 loss had no discernible impact on either endocytosis or phagocytosis in mouse embryo-derived fibroblasts and macrophages, respectively. Similarly, actin cytoskeletal organization, proliferation, and apoptosis in embryo fibroblasts were all unaffected by Bin1 loss. In vivo, however, Bin1 loss resulted in perinatal lethality. Bin1 has been reported to affect muscle cell differentiation and T-tubule formation. No striking histological abnormalities were evident in skeletal muscle of Bin1 null embryos, but severe ventricular cardiomyopathy was observed in these embryos. Ultrastructurally, myofibrils in ventricular cardiomyocytes of Bin1 null embryos were severely disorganized. These results define a developmentally critical role for the Bin1 gene in cardiac muscle development.