Purchase this article with an account.
Helen T. Michael, Cari Graff-Cherry, Sung Chin, Corinne Rauck, Amelework D. Habtemichael, Patricia Bunda, Tunde Smith, Maria M. Campos, Kapil Bharti, Heinz Arnheiter, Glenn Merlino, Chi-Ping Day; Partial Rescue of Ocular Pigment Cells and Structure by Inducible Ectopic Expression of Mitf-M in MITF-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2018;59(15):6067-6073. doi: https://doi.org/10.1167/iovs.18-25186.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Complete deficiency of microphthalmia transcription factor (MITF) in Mitfmi-vga9/mi-vga9 mice is associated with microphthalmia, retinal dysplasia, and albinism. We investigated the ability of dopachrome tautomerase (DCT) promoter-mediated inducible ectopic expression of Mitf-M to rescue these phenotypic abnormalities.
A new mouse line was created with doxycycline-inducible ectopic Mitf-M expression on an Mitf-deficient Mitfmi-vga9 background (DMV mouse). Adult DMV mice were phenotypically characterized and tissues were collected for histology, immunohistochemistry, and evaluation of Mitf, pigmentary genes, and retinal pigment epithelium (RPE) gene expression.
Ectopic Mitf-M expression was specifically induced in the eyes, but was not detected in the skin of DMV mice. Inducible expression of Mitf-M partially rescued the microphthalmia, RPE structure, and pigmentation as well as a subset of the choroidal and iris melanocytes but not cutaneous melanocytes. RPE function and vision were not restored in the DMV mice.
Ectopic expression of Mitf-M during development of Mitf-deficient mice is capable of partially rescuing ocular and retinal structures and uveal melanocytes. These findings provide novel information about the roles of Mitf isoforms in the development of mouse eyes.
This PDF is available to Subscribers Only