Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development

Six4 is a member of the Sh family genes, homologues of Drosophila melanogas ter sine oculis. The gene is thought to be involved in neurogenesis, myogen esis, and development of other organs, based on its specific expression in certain neuronal cells of the developing embryo and in adult skeletal muscl es. To elucidate the biological roles of Six4, we generated Six4-deficient mice by replacing the Six homologous region and homeobox bg the beta -galac tosidase gene, 5-Bromo-4-chloro-3-indolyl-beta -D-galactopyranoside stainin g of the heterozygous mutant embryos revealed expression of Six4 in cranial and dorsal root ganglia, somites, otic and nasal placodes, branchial arche s, Rathke's pouch, apical ectodermal ridges of limb buds, and mesonephros. The expression pattern was similar to that of Six1 except at the early stag e of embryonic day 8.5. Six4-deficient mice were born according to the Mend elian rule with normal gross appearance and were fertile. No hearing defect s were detected. Six4-deficient embryos showed no morphological abnormaliti es, and the expression patterns of several molecular markers, e.g., myogeni n and NeuroD3 (neurogenin1), were normal. Our results indicate that Six4 is not essential for mouse embryogenesis and suggest that other members of th e Six family seem to compensate for the loss of Six4.