Localization of caspase 12 in masseter muscle of mdx mice during regeneration

S. Abe
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Abstract

The mdx mouse, a model of muscular dystrophy, lacks dystrophin, a cell membrane protein. It is known that this lack of dystrophin results in muscle fiber necrosis from 2 weeks after birth, and the majority of necrotic fibers are replaced by regenerated fibers by 4 weeks of age. Recent studies reported the detection of mitochondrial and endoplasmic reticulum stress proteins during muscle fiber necrosis in mdx mice, but did not histologically localize them to determine the timing of their expression during the process from cell necrosis to regeneration. Therefore, in this study, we investigated histological localization and gene-level expression in the mdx mouse masseter muscle of caspase-12 protein (among the caspases, which are cell stress-related genes) involved in the endoplasmic reticulum stress pathway. We observed caspase-12 expression in muscle cells that seemed to be in the process of necrosis in the mdx mouse masseter muscle at 2 weeks after birth, but not in regenerated muscle cells with centrally located nuclei observed at 3 to 4 weeks of age. These results suggest that due to the lack of dystrophin, it becomes difficult for muscle cells to maintain their morphology, and endoplasmic reticulum stress occurs to maintain cell morphology during the process of cell necrosis.
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mdx小鼠咬肌再生过程中caspase 12的定位
mdx小鼠是一种肌肉萎缩模型,缺乏肌营养不良蛋白,一种细胞膜蛋白。众所周知,这种肌营养不良蛋白的缺乏导致出生后2周的肌纤维坏死,大部分坏死纤维在4周龄时被再生纤维所取代。最近的研究报道了mdx小鼠肌纤维坏死过程中线粒体和内质网应激蛋白的检测,但没有对它们进行组织学定位,以确定它们在细胞坏死到再生过程中的表达时间。因此,在本研究中,我们研究了参与内质网应激途径的caspase-12蛋白(caspase是细胞应激相关基因中的一种)在mdx小鼠咬肌中的组织定位和基因水平表达。我们在出生后2周的mdx小鼠咬肌中观察到caspase-12在肌细胞中表达,这些肌细胞似乎处于坏死过程中,但在3至4周龄的再生肌细胞中没有caspase-12的表达。这些结果表明,由于缺乏肌营养不良蛋白,肌肉细胞难以维持其形态,在细胞坏死过程中发生内质网应激以维持细胞形态。
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