Development of skeletal muscles in transforming growth factor-beta 1 (TGF-β1) null-mutant mice

Fetal transforming growth factor-beta 1 (TGF-beta 1) has been postulated to regulate the onset of myotube formation and/or pattern formation in developing skeletal muscles. In apparent contradiction of these hypotheses, the development of the extensor digitorum longus and soleus in TGF-beta 1 null-mutant muscle was normal, The onset of secondary myotube formation, the numbers of myotubes formed, the proportion of fast and slow fibers, and the patterns of fiber types and connective tissues were essentially identical in TGF-beta 1((+/+)) and TGF-beta 1((-/-)) mice. A portion of the TGF-beta 1 in skeletal muscles is derived from the mother, via the placenta. This maternal-derived TGF-beta 1 was also not essential for the development of skeletal muscles, as the characteristics of pups born to a TGF-beta 1((-/-)) mother were normal. TGF-beta((-/-)) mice die at weaning due to a generalized autoimmune attack This postnatal death was circumvented by breeding the TGF-beta 1 null mutation into nude mice (Whn((-/-))). Like many other strains of TGF-beta((-/-)) mice, extensive loss of Whm((-/-)), TGF-beta 1((-/-)) embryos occurred in utero, However, a portion of the Whn((-/-)), TGF-beta 1((-/-)) mice survived past weaning, remained healthy, and were fertile. The TGF-beta 1((-/-)) x Whn((-/-)) mouse thus represents a valuable tool for the study of the function of TGF-beta 1 in the adult, including its putative role as a pregnancy-related hormone. Dev Dyn 2000;211:250-256. (C) Wiley-Liss, Inc.