engleski

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 mitoge‐ nome 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 con‐ firmed by Sanger sequencing across multiple generations, whereas no single analysis revealed evi‐ dence of heteroplasmy. A closer clinical examination of one cow with the T10432C mutation re‐ vealed exophthalmos, whereas histopathological examination revealed retinal ablations, subretinal oedema, and haemorrhage. The results of these analyses confirm the presence of mitochondrial mu‐ tation 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 ani‐ mal model that can improve our understanding of the pathogenesis of LHON and other mitochon‐ driopathies.

animal model ; retinal ablation ; cattle ; detrimental mutations ; LHON ; mitogenome

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