# Canine MPV17 truncation without clinical manifestations

## TL;DR

A MPV17 gene mutation in dogs causes protein truncation but no obvious health issues, suggesting species differences in disease manifestation.

## Contribution

Identifies a MPV17 truncation mutation in dogs with no clinical symptoms, establishing a new large animal model for mitochondrial research.

## Key findings

- A 1-bp insertion in MPV17 exon 4 causes frameshift and protein truncation in dogs.
- MPV17 expression is reduced in homozygous dogs, and the truncated protein is not translated in transfected cells.
- No common phenotypes are observed in affected dogs, despite the mutation being highly enriched in Boxers.

## Abstract

Mitochondrial DNA depletion syndromes (MDS) are often serious autosomal recessively inherited disorders characterized by tissue-specific mtDNA copy number reduction. Many genes, including MPV17, are associated with the hepatocerebral form of MDS. MPV17 encodes for a mitochondrial inner membrane protein with a poorly characterized function. Several MPV17 mutations have been reported in association with a heterogeneous group of early-onset manifestations, including liver disease and neurological problems. Mpv17-deficient mice present renal and hearing defects. We describe here a MPV17 truncation mutation in dogs. We found a 1-bp insertion in exon 4 of the MPV17 gene, resulting in a frameshift and early truncation of the encoded protein. The mutation halves MPV17 expression in the lymphocytes of the homozygous dogs and the truncated protein is not translated in transfected cells. The insertion mutation is recurrent and exists in many unrelated breeds, although is highly enriched in the Boxer breed. Unexpectedly, despite the truncation of MPV17, we could not find any common phenotypes in the genetically affected dogs. The lack of observable phenotype could be due to a late onset, mild symptoms or potential tissue-specific compensatory mechanisms. This study suggests species-specific differences in the manifestation of the MPV17 defects and establishes a novel large animal model to further study MPV17 function and role in mitochondrial biology.