Mice with mutations at the microphthalmia(mi) locus have some or all of the following defects: loss of pigmentation, reduced eye size, failureof secondary bone resorption, reduced numbers of mast cells, and early onset of deafness. Using a transgenic insertional mutation at this locus, we have identified a gene whose expression is disrupted in transgenic animals. This gene encodes a novel member of the basic-helix-loop helix-ieucine zipper (bHLH-ZIP) protein family of transcription factors, is altered in mice carrying two independent mi alleles (mi and mi”), and is expressed in the developing eye, ear, and skin, all anatomical sites affected by mi. The multiple spontaneous and induced mutations available at mi provide a unique biological resource for studying the role of a bHLH-ZIP protein in mammalian development. introduction

Much of our knowledge on the function of genes in mammalian development and adulthood has come from the molecular analysis of spontaneous or induced mutations. Mutations affecting pigmentation of the coat can be identified easily, and it is not surprising that in mice alone, more than 70 loci have been described that are involved in determining coat color. Analysis of some of these mutations has revealed that genes controlling pigmentation may also regulate other developmental processes such as neural development, bone formation, hematopoiesis, and fertility.