期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 122, 期 12, 页码 4412-4423出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI63765
关键词
-
资金
- Canadian Institutes of Health Research
- Association Francaise Contre les Myopathies
ATR-X syndrome is a severe intellectual disability disorder caused by mutations in the ATRX gene. Many ancillary clinical features are attributed to CNS deficiencies, yet most patients have muscle hypotonia delayed ambulation, or kyphosis, pointing to an underlying skeletal muscle defect Here, we identified a cell-intrinsic requirement for Atrx in postnatal muscle growth and regeneration in mice. Mice with skeletal muscle=specific Atrx conditional knockout (Atrx cKO mice) were viable, but by 3 weeks of presented hallmarks of underdeveloped musculature, including kyphosis, 20% reduction in body mass, and 34% reduction in muscle fiber caliber. Atrx cKO mice also demonstrated a marked regeneration deficit that was not due to fewer resident satellite cells or their inability to terminally differentiate. However, activation of Atrx-null satellite cells from isolated muscle fibers resulted in a 9-fold reduction in myoblast expansion, caused by delayed progression through mid to late S phase. While in S phase, Atrx colocalized specifically to late replicating chromatin, and its loss resulted in rampant signs of genomic instability These observations support a model in which Atrx maintains chromatin integrity during the rapid developmental growth of a tissue.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据