Regulation of lens fiber cell differentiation by transcription factor c-Maf

To elucidate the regulatory mechanisms underlying lens development, we sear ched for members of the large Maf family, which are expressed in the mouse lens, and found three, c-Maf, MafB, and Nrl. Of these, the earliest factor expressed in the lens was c-Maf. The expression of c-Maf was most prominent in lens fiber cells and persisted throughout lens development. To examine the functional contribution of c-Maf to lens development, we isolated genom ic clones encompassing the murine c-maf gene and carried out its targeted d isruption. Insertion of the beta-galactosidase (lacZ) gene into the c-maf l ocus allowed visualization of c-Maf accumulation in heterozygous mutant mic e by staining for LacZ activity. Homozygous mutant embryos and newborns lac ked normal lenses. Histological examination of these mice revealed defectiv e differentiation of lens fiber cells. The expression of crystallin genes w as severely impaired in the c-maf-null mutant mouse lens. These results dem onstrate that c-Maf is an indispensable regulator of lens differentiation d uring murine development.