Mitfmi/+ as a new mouse model of cone dystrophy

Abstract

Purpose: Mutations in the Mitf gene can lead to hypopigmentation, microphthalmia, retinal degeneration, deafness and blindness1. We have previously shown that RPE function and structure is affected in mice with various mutations in the Mitf gene, which is expressed specifically in the RPE, resulting in some cases in retinal degeneration2. The current study is the first of its kind to analyse visual and retinal function in Mitfmi/+ mice. Methods: Mitfmi/+ and C5BL/6 J (as control) mice were used in this study. All mice were 1‐ and 3‐months old. Electroretinography (ERG) was performed under both dark‐ and light‐adapted conditions, along with fundus photography from anaesthetised mice. The ERG dark‐adapted a‐, b‐ and c‐waves were analysed. Light‐adapted b‐wave amplitude was analysed. Fundus photography was performed to visualize and compare fundus images from wild type and Mitfmi/+ mice. Results: Light‐adapted a‐wave amplitude was significant lower in 3‐month‐old mutants (7.34 ± 1.34 μV, 6.72 ± 1.19 μV, 8.58 ± 1.03 μV; p < 0.05) compared to wild type mice at 3, 5 and 7 cd*sec/m2 respectively. Light‐adapted b‐wave amplitude was also significantly reduced in 3‐month‐old mutants (22.13 ± 0.95 μV, 35.09 ± 2.72 μV, 57.715 ± 5.17 μV, 66.16 ± 4.48 μV, 85.87 ± 4.27 μV; p < 0.05) compared to control animals at all luminance tested. Interestingly, ERG c‐wave amplitude was significantly lower in 1‐month‐old Mitfmi/+ (150.80 ± 11.91 μV; p < 0.05) compared to control mice at 10 cd*sec/m2 light intensity. Progressive hyper‐ and hypopigmentation areas were found in the fundi from the mutants. Conclusions: Retinal function was greatly affected in Mitfmi/+ mutant mice. Significantly lower c‐wave response and hypopigmentation provide evidence for severe RPE pigmentation and likely dysfunction as well in the mutants at 1‐month‐old. Furthermore, lower light‐adapted a‐ and b‐ wave responses indicates selective cone‐dystrophy in this heterozygous mutation in the Mitf gene. References 1 Steingrímsson E et al. Annu Rev Genet, 2004; 38:365–411. 2 García‐Llorca A et al. Sci Rep, 2019; 28; 9(1):15386.