Idiopathic weight reduction in mice deficient in the high-mobility-group transcription factor Sox8

Sox8, Sox9, and Sox10 constitute subgroup E within the Sox family of transc ription factors. Many Sox proteins are essential regulators of development. Sox9, for instance, is required for chondrogenesis and male sex determinat ion; Soxl0 plays key roles in neural crest development and peripheral gliog enesis. The function of Sox8 has not been studied so far. Here, we generate d mice deficient in this third member of subgroup E. In analogy to the case for the related Sox9 and Sox10, we expected severe developmental defects i n these mice. Despite strong expression of Sox8 in many tissues, including neural crest, nervous system, muscle, cartilage, adrenal gland, kidney, and testis, homozygous mice developed normally in utero, were born at Mendelia n frequencies, and were viable. A substantial reduction in weight was obser ved in these mice; however, this reduction was not attributable to signific ant structural deficits in any of the Sox8-expressing tissues. Because of f requent coexpression with either Sox9 or Sox10, the mild phenotype of Sox8- deficient mice might at least in part be due to functional redundancy betwe en group E Sox proteins.