International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

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POSTER 11 - ECTOPIC SOX10 EXPRESSION INDUCES ECTOPIC PIGMENT FORMATION IN NEURONAL CELL TYPES

Hakami R M
National Institutes of Health, NHGRI

Co-Authors: 2) Arnheiter H, 1) Pavan W J
Institutions: 1) National Institutes of Health, NHGRI, 2) National Institutes of Health, NINDS

Sox10 is a high-mobility-group transcription factor critical for the development of glia and melanocytes. Mutations in Sox10 have been associated with neurocristopathies in Waardenburg syndrome Type IV patients, and in the murine mutant, Dominant megacolon. While Sox10 is clearly necessary for glial and pigmented melanocyte formation, it is unknown whether it is also sufficient to promote their differentiation. We have therefore constructed and characterized Sox10 transgenic mice in which a functional Sox10 transgene is regulated by the Dopachrome Tautomerase (Dct) promoter. Embryonic Dct is expressed in Sox10+ cells (melanoblasts) and Sox10- cells (retinal pigment epithelium (RPE) and the dorsal neuroepithelium of the brain). Dct-Sox10 transgenic mice present with small eyes, cataracts, circling and hyperkinetic behavior, tremors, severe imbalance, and gradual coat color loss. Postnatal eyes show age-dependent disorganization of the neural retina (NR) and localized RPE thickening. Most significantly, in the homozygotes, part of the basal ganglion layer of the NR that is positive for the Sox10 transgene expression produces pigment. Since Sox10 directly activates Mitf, a transcription factor critical for melanocyte and RPE development, we tested for correction of the eye defects by introducing one of two Mitf alleles, one a regulatory mutant and the other a null allele (rw or vga-9). In 5-10 animals examined in each case the cataracts, NR disorganization, and decreased eye size were corrected in Dct-Sox10, Mitf double heterozygotes. These findings suggest a model in which ectopic Sox10 expression activates the Mitf pathway, resulting in eye phenotypes.