The consequences of mitochondrial T10432C mutation in Cika cattle : A “potential” model for Leber’s hereditary optic neuropathy

Novosel, Dinko (author), Brajkovic, Vladimir (author), Simčič, Mojca (author), Zorc, Minja (author), Švara, Tanja (author), Branović-Čakanić, Karmen (author), Jungić, Andreja (author), Logar, Betka (author), Čubrić Čurik, Vlatka (author), Dovč, Peter (author), Čurik, Ino (author)

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.

• Language: English
• Keywords: animal model, retinal ablation, cattle, detrimental mutations, LHON, mitogenome
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty; VF - Veterinary Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 15 str.
• Numbering: Vol. 23, iss. 11, art. 6335
• PID: 20.500.12556/RUL-138112
• UDC: 575:636.2
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms23116335
• COBISS.SI-ID: 110712835
• Publication date in RUL: 11.07.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: govedo, genetika, živalski modeli, mitohondrijski genom, Leberjeva dedna optična nevropatija, LHON

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Croatian Science Foundation
• Project number: ANAGRAMS-IP-2018-01-8708

• Funder: Other - Other funder or multiple funders
• Funding programme: Croatian Science Foundation
• Project number: MITOTAUROMICSIP-11-2013_9070