Age-dependent changes in the electroretinograms in mice with various mutations in the Microphthalmia transcription factor (Mitf) gene

Abstract

The microphthalmia-associated transcription factor gene (Mitf) is associated with congenital development in the retina, affecting visual ability of the eye. Most severe Mitf gene expression causes microphthalmia, hypopigmentation and blindness. Similar phenotypes can be found in the Waardenburg and Tietz syndrome in humans. The purpose of this study was to examine the role Mitf plays in age-dependent development in the retina, one month after birth. Four Mitf mutant mice ranging in mutational severity were selected, from the weakest phenotype used (Mitfmi-enu22) to the most severe one used (Mitfmi-wh/Mitfmi), with all of them possessing loss-of-function allele, and with two of them also showing intra-allelic complementation. One of the intra-allelic complementation mutant has proved to be suitable model for Waardenburg syndrome in humans. Retinal function was analyzed via electroretinography (ERG) as an evaluation of how the MITF protein affects retinal and visual development after birth. In addition, fundus images were taken and analyzed. All data from one month old mutants were compared to one month old wild type mice (C57BL/6J). To assess age-dependent development, further comparison to already existing data from same mutations in three months old mice was made. It was hypothesized that since the most severe genotypes used in this study possessed one allele with complementary ability, such allele mutation could serve as a protective factor in age-dependent developmental loss in vision. Existing results from three month old mutants possessing the complementary allele show blindness in both mutations. In this study however, results for same mutations indicate that those mice have vision one month after birth. Age-related comparison further suggested a fast degeneration in the RPE of those mutants, and a possibility of fast rod-cone dystrophy in the most severe mutant mouse. It was also hypothesized that similar degenerational processes have already began in the less severe mutant mice at one month old. Since those mutants have vision at both one and three months old, the degeneration process seems to happen at much slower rate. In the younger mice, the medians of the groups, measured in amplitudes, differed significantly among all light intensities used.