20.500.12556/RUL-138112 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 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. animal model retinal ablation cattle detrimental mutations LHON mitogenome govedo genetika živalski modeli mitohondrijski genom Leberjeva dedna optična nevropatija LHON true false true Angleški jezik Slovenski jezik Članek v reviji 2022-07-11 10:38:20 2022-07-11 10:38:21 2022-09-15 04:16:19 0000-00-00 00:00:00 2022 0 0 15 str. iss. 11, art. 6335 Vol. 23 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575:636.2 1422-0067 10.3390/ijms23116335 110712835 ijms-23-06335-v2.pdf ijms-23-06335-v2.pdf 1 4ABEACDAF3E925B0CBEE3939A4A93FA0 3789182af80a184e6319b3fde7adf4ca8eef6512828ee9d19da731ac6f3a7cce 8ec89f08-00f9-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=158325 https://www.mdpi.com/1422-0067/23/11/6335 1 984aaccf-00f4-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=158324 Biotehniška fakulteta Veterinarska fakulteta 0 0 0