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.