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Merck

The histone code reader Spin1 controls skeletal muscle development.

Cell death & disease (2017-11-24)
Holger Greschik, Delphine Duteil, Nadia Messaddeq, Dominica Willmann, Laura Arrigoni, Manuela Sum, Manfred Jung, Daniel Metzger, Thomas Manke, Thomas Günther, Roland Schüle
摘要

While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1M5 mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1M5 mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1M5 mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1M5 fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1M5 mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease.

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胶原酶 来源于溶组织梭菌, for general use, Type I, ≥125 CDU/mg solid
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布安溶液, histological fixative
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Schiff′s试剂
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单克隆抗肌球蛋白(骨骼肌快肌) 小鼠抗, clone MY-32, ascites fluid
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单克隆抗肌球蛋白(骨骼,缓慢) 小鼠抗, clone NOQ7.5.4D, ascites fluid
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苏木素溶液,Gill 3号
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曙红Y溶液,酒精,含荧光桃红
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高碘酸 溶液, 1 g/dL in deionized water
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TCF-4抗体,克隆6H5-3, clone 6H5-3, Upstate®, from mouse