MOLECULAR-BASIS OF MOUSE MICROPHTHALMIA (MI) MUTATIONS HELPS EXPLAIN THEIR DEVELOPMENTAL AND PHENOTYPIC CONSEQUENCES

Mutations in the mouse microphthalmia (mi) gene affect the development of a number of cell types including melanocytes, osteoclasts and mast cells. Recently, mutations in the human mi gene (MITF) were found in patients with Waardenburg Syndrome type 2 (WS2), a dominantly inherite d syndrome associated with hearing loss and pigmentary disturbances. W e have characterized the molecular defects associated with eight murin e mi mutations, which vary in both their mode of inheritance and in th e cell types they affect. These molecular data, combined with the exte nsive body of genetic data accumulated for murine mi, shed light on th e phenotypic and developmental consequences of mi mutations and offer a mouse model for WS2.