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The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy
While mitogenome mutations leading to pathological manifestations are rare, more than 200 such mutations have been described in humans. In contrast, pathogenic mitogenome mutations are rare in domestic animals and have not been described at all in cattle. In the small local Slovenian cattle breed Ci...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181260/ https://www.ncbi.nlm.nih.gov/pubmed/35683014 http://dx.doi.org/10.3390/ijms23116335 |
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author | Novosel, Dinko Brajković, Vladimir Simčič, Mojca Zorc, Minja Svara, Tanja Cakanic, Karmen Branovic Jungić, Andreja Logar, Betka Cubric-Curik, Vlatka Dovc, Peter Curik, Ino |
author_facet | Novosel, Dinko Brajković, Vladimir Simčič, Mojca Zorc, Minja Svara, Tanja Cakanic, Karmen Branovic Jungić, Andreja Logar, Betka Cubric-Curik, Vlatka Dovc, Peter Curik, Ino |
author_sort | Novosel, Dinko |
collection | PubMed |
description | While mitogenome mutations leading to pathological manifestations are rare, more than 200 such mutations have been described in humans. In contrast, pathogenic mitogenome mutations are rare in domestic animals and have not been described at all in cattle. In the small local Slovenian cattle breed Cika, we identified (next-generation sequencing) two cows with the T10432C mitogenome mutation in the ND4L gene, which corresponds to the human T10663C mutation known to cause Leber’s hereditary optic neuropathy (LHON). Pedigree analysis revealed that the cows in which the mutation was identified belong to two different maternal lineages with 217 individual cows born between 1997 and 2020. The identified mutation and its maternal inheritance were confirmed by Sanger sequencing across multiple generations, whereas no single analysis revealed evidence of heteroplasmy. A closer clinical examination of one cow with the T10432C mutation revealed exophthalmos, whereas histopathological examination revealed retinal ablations, subretinal oedema, and haemorrhage. The results of these analyses confirm the presence of mitochondrial mutation T10432C with homoplasmic maternal inheritance as well as clinical and histopathological signs similar to LHON in humans. Live animals with the mutation could be used as a suitable animal model that can improve our understanding of the pathogenesis of LHON and other mitochondriopathies. |
format | Online Article Text |
id | pubmed-9181260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91812602022-06-10 The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy Novosel, Dinko Brajković, Vladimir Simčič, Mojca Zorc, Minja Svara, Tanja Cakanic, Karmen Branovic Jungić, Andreja Logar, Betka Cubric-Curik, Vlatka Dovc, Peter Curik, Ino Int J Mol Sci Article While mitogenome mutations leading to pathological manifestations are rare, more than 200 such mutations have been described in humans. In contrast, pathogenic mitogenome mutations are rare in domestic animals and have not been described at all in cattle. In the small local Slovenian cattle breed Cika, we identified (next-generation sequencing) two cows with the T10432C mitogenome mutation in the ND4L gene, which corresponds to the human T10663C mutation known to cause Leber’s hereditary optic neuropathy (LHON). Pedigree analysis revealed that the cows in which the mutation was identified belong to two different maternal lineages with 217 individual cows born between 1997 and 2020. The identified mutation and its maternal inheritance were confirmed by Sanger sequencing across multiple generations, whereas no single analysis revealed evidence of heteroplasmy. A closer clinical examination of one cow with the T10432C mutation revealed exophthalmos, whereas histopathological examination revealed retinal ablations, subretinal oedema, and haemorrhage. The results of these analyses confirm the presence of mitochondrial mutation T10432C with homoplasmic maternal inheritance as well as clinical and histopathological signs similar to LHON in humans. Live animals with the mutation could be used as a suitable animal model that can improve our understanding of the pathogenesis of LHON and other mitochondriopathies. MDPI 2022-06-06 /pmc/articles/PMC9181260/ /pubmed/35683014 http://dx.doi.org/10.3390/ijms23116335 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Novosel, Dinko Brajković, Vladimir Simčič, Mojca Zorc, Minja Svara, Tanja Cakanic, Karmen Branovic Jungić, Andreja Logar, Betka Cubric-Curik, Vlatka Dovc, Peter Curik, Ino The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy |
title | The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy |
title_full | The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy |
title_fullStr | The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy |
title_full_unstemmed | The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy |
title_short | The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy |
title_sort | consequences of mitochondrial t10432c mutation in cika cattle: a “potential” model for leber’s hereditary optic neuropathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181260/ https://www.ncbi.nlm.nih.gov/pubmed/35683014 http://dx.doi.org/10.3390/ijms23116335 |
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