Electroretinographic assessment of retinal function in microphthalmia mutant mice

The purpose of this study was to examine the effects of mutations in the mouse (Mus musculus) multi-allelic microphthalmia transcription factor (Mitf) gene on retinal function. Mitf mice provide a rare opportunity to assess retinal degeneration caused by defective retinal pigment epithelium (RPE). Electroretinography (ERG) was used to evaluate the functional state of the retina and to determine the role of the Mitf gene in visual function. Corneal ERGs were recorded with a steel wire in response to white flashes of light. Homozygous Mitf(Mi-wh)/Mitf(Mi-wh), Mitf(mi-sp)/Mitf(mi-sp) Mitf(mi-bws)/Mitf(mi-bws) and wild type mice in addition to Mitf(Mi-wh)/Mitf(mi-sp) compound heterozygous mutants were studied at 16 weeks of age. Although each animal was only tested once, multiple animals of each genotype were tested. The ERGs of Mitf(mi-sp)/Mitf(mi-sp) were found to be normal. All components of the ERGs of Mitf(mi-bws)/Mitf(mi-bws) mice were normal except the photopic b-wave and the scotopic c-wave, which were reduced in amplitude. The ERGs of Mitf(Mi-wh)/Mitf(Mi-wh) mice suggest they are probably blind. On the other hand, ERGs from Mitf(Mi-wh)/Mitf(mi-sp) mice were reduced in amplitude and delayed, indicating an RPE/photoreceptor defect. At 16 weeks post partum, Mitf(Mi-wh)/Mitf(mi-sp) mutants show evidence of rod-cone dystrophy. Surprisingly, Mitf(mi-bws)/Mitf(mi-bws) mice, which have a similar phenotype as Mitf(mi-vit) mice with respect to coat color and eye development, show mostly normal ERGs. The reduced scotopic c-wave in Mitf(mi-bws)/Mitf(mi-bws) mice, without reduction in the scotopic a-wave indicates an RPE defect without photoreceptor involvement in these mice.