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Expression pattern of mRNA A and mRNA B of alpha sarcoglycan gene during mouse embryonic development and regulation of their expression by myogenic and cardiogenic transcription factors.

Dev. Dyn.2014 Nov;243(11):1416-28. doi:10.1002/dvdy.24175. Epub 2014 Aug 25
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摘要


BACKGROUND:Type 2D limb-girdle muscular dystrophy (LGM2D) is a progressive disorder caused by mutations in the alpha sarcoglycan (α-SG) gene. In mice, the α-SG gene contains two promoters that regulate the expression of two different mRNAs (A and B). However, their gene expression pattern during embryonic development has not been explored and their regulation by myogenic and cardiogenic transcription factors has been only partially studied. RESULTS:During embryonic development, mRNA A and B of α-SG gene were initially detected in hypaxial muscles, heart, stomach, tongue, and mesenchymal cells, which surround the dorsal region of the somites. Moreover, mRNA B was exclusively expressed in the floor plate and notochord and in the interdigits of limbs. In vitro, MyoD and myogenin positively regulated the transcription of mRNA B during skeletal myogenesis, whereas mRNA A was activated only for MyoD in differentiated skeletal muscle. In addition, Gata-4 together with Mef2c may regulate the expression of mRNA B in heart development, whereas Nkx2.5 and myocardin may activate expression of mRNA A in the differentiated cardiomyocyte. CONCLUSIONS:The differential expression of α-SG mRNAs during mouse embryonic development may be a consequence of the differential regulation of both promoters by myogenic and cardiogenic factors.

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