Development of skeletal muscles in transforming growth factor-beta 1 (TGF-beta1) null-mutant mice.

Fetal transforming growth factor-beta 1 (TGF-beta1) 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-beta1 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-beta1(+/+) and TGF-beta1(-/-) mice. A portion of the TGFbeta1 in skeletal muscles is derived from the mother, via the placenta. This maternal-derived TGF-beta1 was also not essential for the development of skeletal muscles, as the characteristics of pups born to a TGF-beta1(-/-) mother were normal TGF-beta1(-/-) mice die at weaning due to a generalized autoimmune attack. This postnatal death was circumvented by breeding the TGF-beta1 null mutation into nude mice (Whn(-/-)). Like many other strains of TGF-beta1(-/-) mice, extensive loss of Whn(-/-), TGF-beta1(-/-) embryos occurred in utero. However, a portion of the Whn(-/-), TGF-beta1(-/-) mice survived past weaning, remained healthy, and were fertile. The TGF-beta1(-/-) x Whn(-/-) mouse thus represents a valuable tool for the study of the function of TGF-beta1 in the adult, including its putative role as a pregnancy-related hormone.