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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 mu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817937/ https://www.ncbi.nlm.nih.gov/pubmed/31659211 http://dx.doi.org/10.1038/s41598-019-51819-0 |
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author | García-Llorca, Andrea Aspelund, Snaefridur Gudmundsdottir Ogmundsdottir, Margret Helga Steingrimsson, Eiríkur Eysteinsson, Thor |
author_facet | García-Llorca, Andrea Aspelund, Snaefridur Gudmundsdottir Ogmundsdottir, Margret Helga Steingrimsson, Eiríkur Eysteinsson, Thor |
author_sort | García-Llorca, Andrea |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6817937 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68179372019-11-01 The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function García-Llorca, Andrea Aspelund, Snaefridur Gudmundsdottir Ogmundsdottir, Margret Helga Steingrimsson, Eiríkur Eysteinsson, Thor Sci Rep Article 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. Nature Publishing Group UK 2019-10-28 /pmc/articles/PMC6817937/ /pubmed/31659211 http://dx.doi.org/10.1038/s41598-019-51819-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article García-Llorca, Andrea Aspelund, Snaefridur Gudmundsdottir Ogmundsdottir, Margret Helga Steingrimsson, Eiríkur Eysteinsson, Thor The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function |
title | The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function |
title_full | The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function |
title_fullStr | The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function |
title_full_unstemmed | The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function |
title_short | The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function |
title_sort | microphthalmia-associated transcription factor (mitf) gene and its role in regulating eye function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817937/ https://www.ncbi.nlm.nih.gov/pubmed/31659211 http://dx.doi.org/10.1038/s41598-019-51819-0 |
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