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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...

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Autores principales: Novosel, Dinko, Brajković, Vladimir, Simčič, Mojca, Zorc, Minja, Svara, Tanja, Cakanic, Karmen Branovic, Jungić, Andreja, Logar, Betka, Cubric-Curik, Vlatka, Dovc, Peter, Curik, Ino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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