Conditional knockout of pik3c3 causes a murine muscular dystrophy.
Conditional knockout of pik3c3 causes a murine muscular dystrophy.
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pik3c3 的条件性敲除会导致小鼠肌营养不良症。
DOI：
10.1016/j.ajpath.2014.02.012
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Dowling,JamesJ
中科院分区：
文献类型：
--
作者：
Reifler,Aaron;Li,Xingli;Archambeau,AshleyJ;McDade,JoelR;Sabha,Nesrin;Michele,DanielE;Dowling,JamesJ
Abnormalities in phosphoinositide metabolism are an emerging theme in human neurodegenerative disease. Myotubular myopathy is a prototypical disorder of phosphoinositide dysregulation that is characterized by profound muscle pathology and weakness and that is caused by mutations inMTM1, which encodes a phosphatase that targets 3-position phosphoinositides, including phosphatidylinositol 3-phosphate. Although the association between MTM1 and muscle disease has become increasingly clarified, the normal role(s) of phosphatidylinositol 3-phosphate metabolism in muscle development and homeostasis remain poorly understood. To begin to address the function of phosphatidylinositol 3-phosphate in skeletal muscle, we focused on the primary kinase responsible for its production, and created a muscle-specific conditional knockout of the class III phosphatidylinositol 3-kinase,Pik3c3. Muscle-specific deletion ofPik3c3did not disturb embryogenesis or early postnatal development, but resulted in progressive disease characterized by reduced activity and death by 2 months of age. Histopathological analysis demonstrated changes consistent with a murine muscular dystrophy. Examination for cellular mechanism(s) responsible for the dystrophic phenotype revealed significant alterations in the autophagolysosomal pathway with mislocation of known dystrophy proteins to the lysosomal compartment. In all, we present the first analysis ofPik3c3in skeletal muscle, and report a novel association between deletion ofPik3c3and muscular dystrophy.
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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
影响因子：
16
作者：
Bruning, JC;Michael, MD;Kahn, CR
通讯作者：
Kahn, CR
PtdIns5P 通过进化进行调控：在膜运输中的作用？
DOI：
--
发表时间：
2008
期刊：
TIBS -Trends in Biochemical Sciences. Regular ed
影响因子：
--
作者：
O. Lecompte;O. Poch;J. Laporte
通讯作者：
J. Laporte
DOI：
10.1073/pnas.1205305109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Willinger, Tim;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
29
作者：
Mammucari, Cristina;Milan, Giulia;Sandri, Marco
通讯作者：
Sandri, Marco