The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function
Autor: | Margret H. Ogmundsdottir, Andrea García-Llorca, Snaefridur Gudmundsdottir Aspelund, Thor Eysteinsson, Eiríkur Steingrímsson |
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Přispěvatelé: | Læknadeild (HÍ), Faculty of Medicine (UI), Lífeðlisfræðistofnun (HÍ), Institute of Physiology (UI), Lífvísindasetur (HÍ), Biomedical Center (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Heterozygote
Mutant lcsh:Medicine Retinal Pigment Epithelium Biology Compound heterozygosity Article Stökkbreytingar chemistry.chemical_compound Mice medicine Animals Microphthalmos lcsh:Science Microphthalmia-Associated Transcription Factor Multidisciplinary Retinal pigment epithelium Eye Color Molecular medicine integumentary system Homozygote lcsh:R Retinal Vessels Retinal Microphthalmia-associated transcription factor Molecular biology Eye pigmentation eye diseases Mice Inbred C57BL body regions medicine.anatomical_structure chemistry Sensory processing lcsh:Q Augu sense organs Sameindafræði Erg Photopic vision |
Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Publisher's version (útgefin grein). 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 (Mitfmi-vga9/+, Mitfmi-enu22(398)/Mitfmi-enu22(398), MitfMi-Wh/+ and MitfMi-Wh/Mitfmi) 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 Mitfmi-vga9/+ mice. MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice showed large non-pigmented areas. Fluorescent angiography (FA) of all mutants except Mitfmi-vga9/+ mice showed hyperfluorescent areas, whereas FA from both Mitf-Mi-Wh/+ and MitfMi-Wh/Mitfmi mice showed reduced capillary network as well as hyperfluorescent areas. Electroretinogram (ERG) recordings show that MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice are severely impaired functionally whereas the scotopic and photopic ERG responses of Mitfmi-vga9/+ and Mitfmi-enu22(398)/Mitfmi-enu22(398) mice were not significantly different from wild type mice. Histological sections demonstrated that the outer retinal layers were absent from the MitfMi-Wh/+ and MitfMi-Wh/Mitfmi 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. The Icelandic Research Fund, The National University Hospital Research Fund, The Helga Jónsdóttir and Sigurliði Kristjánsson Memorial Fund. |
Databáze: | OpenAIRE |
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