EXPRESSION OF GENES (CAPN3, SGCA, SGCB, AND TTN) INVOLVED IN PROGRESSIVE MUSCULAR-DYSTROPHIES DURING EARLY HUMAN-DEVELOPMENT

The developmental expression pattern of four human genes, three of whi ch are involved in progressive muscular dystrophies, was investigated. The rationale for these experiments is that these patterns might prov ide useful information on the pathophysiology underlying these myopath ies. Despite the presence of overlapping clinical signs, the spatiotem poral expression profiles of the corresponding genes differed widely. Transcripts of alpha-sarcoglycan (SGCA) were visible as soon as myotom es were formed, and constitute, together with titin transcripts, preco cious muscular system landmarks. beta-sarcoglycan (SGCB) was initially transcribed in a ubiquitous manner, and, toward the second part of th e embryonic period, became specific to striated muscle, heart, and the central nervous system. Whereas titin (TTN) transcription and transla tion seem to be coupled, for the sarcoglycans, translation seemed rest ricted to skeletal muscle. Calpain3 (CAPN3) RNA was found in only skel etal muscles during the fetal period. It was, however, present earlier in the whole heart, where it selectively disappeared, Finally, eviden ce for differentially spliced calpain3 variants in smooth muscles was also seen. The expression profiles of these genes is suggestive of the ir having a role during myogenesis, knowledge of which could be pertin ent to the understanding of the pathophysiology of the associated dise ases. (C) 1998 Academic Press.