The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function

Mutations in the microphthalmia-associated transcription factor (Mitf) gene can cause retinal pigment epithelium (RPE) and retinal dysfunction and degeneration. We examined retinal and RPE structure and function in 3 month old mice homo- or heterozygous or compound heterozygous for different Mitf mutations (Mitf^mi-vga9/+, Mitf^{mi-enu22(398)}/Mitf^{mi-enu22(398)}, Mitf^Mi-Wh/+ and Mitf^Mi-Wh/Mitf^mi) which all have normal eye size with apparently normal eye pigmentation. Here we show that their vision and retinal structures are differentially affected. Hypopigmentation was evident in all the mutants while bright-field fundus images showed yellow spots with non-pigmented areas in the Mitf^mi-vga9/+ mice. Mitf^Mi-Wh/+ and Mitf^Mi-Wh/Mitf^mi mice showed large non-pigmented areas. Fluorescent angiography (FA) of all mutants except Mitf^mi-vga9/+ mice showed hyperfluorescent areas, whereas FA from both Mitf^-Mi-Wh/+ and Mitf^Mi-Wh/Mitf^mi mice showed reduced capillary network as well as hyperfluorescent areas. Electroretinogram (ERG) recordings show that Mitf^Mi-Wh/+ and Mitf^Mi-Wh/Mitf^mi mice are severely impaired functionally whereas the scotopic and photopic ERG responses of Mitf^mi-vga9/+ and Mitf^{mi-enu22(398)}/Mitf^{mi-enu22(398)} mice were not significantly different from wild type mice. Histological sections demonstrated that the outer retinal layers were absent from the Mitf^Mi-Wh/+ and Mitf^Mi-Wh/Mitf^mi blind mutants. Our results show that Mitf mutations affect eye function, even in the heterozygous condition and that the alleles studied can be arranged in an allelic series in this respect.