Muller Alexander J, Baker Judith F, DuHadaway James B, Ge Kai, Farmer George, Donover P Scott, Meade Raymond, Reid Christian, Grzanna Reinhard, Roach Arthur H, Shah Neelima, Soler Alejandro Peralta, Prendergast George C
DuPont Pharmaceuticals Company, Wilmington, Delaware, USA.
Mol Cell Biol. 2003 Jun;23(12):4295-306. doi: 10.1128/MCB.23.12.4295-4306.2003.
The mammalian Bin1/Amphiphysin II gene encodes an assortment of alternatively spliced adapter proteins that exhibit markedly divergent expression and subcellular localization profiles. Bin1 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.
哺乳动物的Bin1/发动蛋白II基因编码一系列选择性剪接的衔接蛋白，这些蛋白表现出明显不同的表达和亚细胞定位模式。Bin1蛋白参与了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，我们通过小鼠体内的同源重组对其进行了破坏。Bin1基因缺失对小鼠胚胎来源的成纤维细胞和巨噬细胞的内吞作用或吞噬作用分别没有明显影响。同样，胚胎成纤维细胞中的肌动蛋白细胞骨架组织、增殖和凋亡均不受Bin1基因缺失的影响。然而，在体内，Bin1基因缺失导致围产期致死。据报道，Bin1会影响肌肉细胞分化和T小管形成。在Bin1基因敲除胚胎的骨骼肌中未观察到明显的组织学异常，但在这些胚胎中观察到严重的心室心肌病。在超微结构上，Bin1基因敲除胚胎心室心肌细胞中的肌原纤维严重紊乱。这些结果确定了Bin1基因在心肌发育中具有发育关键作用。
