Transient overexpression of the Microphthalmia gene in the eyes of Microphthalmia vitiligo mutant mice

Abstract

The murine microphthalmia gene (Mitf) encodes a basic helix-loop-helix transcription factor thought to regulate transcription of genes encoding proteins of the pigmentation pathway. It may promote pigment cell survival and development. The protein encoded by Mitf appears to be critical for eye development, because mutant alleles demonstrate varying degrees of ocular malformation. One of the mildest of these is the Mitf vitiligo (Mitfvit) mutant allele, which exhibits uneven pigmentation of the retinal pigment epithelium (RPE) and slow, progressive photoreceptor cell loss, eventually leading to blindness. In the present study, the expression of Mitf during early eye development in the Mitfvit mutant was compared with that of pigmented wild type mice. Mitf expression quantified by reverse transcriptase-polymerase chain reaction amplification demonstrated a transient elevation of Mitf between embryonic day 10.5 (E10.5) and E13.5 in the Mitfvit mutant compared with wild type mice. In situ hybridization analysis confirmed this elevation and localized Mitf expression to the neuroepithelium during onset of optic vesicle formation (E9.0-E9.5) and, subsequently, to the RPE during optic cup formation (E10-E11.5) in both mutant and wild type eyes. This is the first report of transient elevation of Mitf in any of the Mitf mutants, and the elevation may be relevant to altered levels of pigmentation proteins as well as to the RPE abnormalities observed in the Mitfvit mutant.