MUTATIONS AT THE MOUSE MICROPHTHALMIA LOCUS ARE ASSOCIATED WITH DEFECTS IN A GENE ENCODING A NOVEL BASIC-HELIX-LOOP-HELIX-ZIPPER PROTEIN

Mice with mutations at the microphthalmia (mi) locus have some or all of the following defects: loss of pigmentation, reduced eye size, fail ure of secondary bone resorption, reduced numbers of mast cells, and e arly onset of deafness. Using a transgenic insertional mutation at thi s locus, we have identified a gene whose expression is disrupted in tr ansgenic animals. This gene encodes a novel member of the basic-helix- loop-helix-leucine zipper (bHLH-ZIP) protein family of transcription f actors, is altered in mice carrying two independent mi alleles (mi and mi(ws)), and is expressed in the developing eye, ear, and skin, all a natomical sites affected by mi. The multiple spontaneous and induced m utations available at mi provide a unique biological resource for stud ying the role of a bHLH-ZIP protein in mammalian development.