Canine MPV17 truncation without clinical manifestations

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Pysyväisosoite

http://hdl.handle.net/10138/159059

Lähdeviite

Hanninen , R L , Ahonen , S , Marquez , M , Myohanen , M J , Hytonen , M K & Lohi , H 2015 , ' Canine MPV17 truncation without clinical manifestations ' , Biology open , vol. 4 , no. 10 , pp. 1253-1258 . https://doi.org/10.1242/bio.013870

Julkaisun nimi: Canine MPV17 truncation without clinical manifestations
Tekijä: Hanninen, Reetta L.; Ahonen, Saija; Marquez, Merce; Myohanen, Maarit J.; Hytonen, Marjo K.; Lohi, Hannes
Tekijän organisaatio: Departments of Faculty of Veterinary Medicine
Research Programs Unit
Research Programme for Molecular Neurology
Veterinary Biosciences
Hannes Tapani Lohi / Principal Investigator
Päiväys: 2015-10-15
Kieli: eng
Sivumäärä: 6
Kuuluu julkaisusarjaan: Biology open
ISSN: 2046-6390
DOI-tunniste: https://doi.org/10.1242/bio.013870
URI: http://hdl.handle.net/10138/159059
Tiivistelmä: 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.
Avainsanat: Dog
mtDNA
MPV17
MITOCHONDRIAL-DNA DEPLETION
HEPATOCEREBRAL FORM
MTDNA DEPLETION
LIVER-FAILURE
GENE MPV17
MUTATION
ENCODES
PROTEIN
DEFICIENCY
METABOLISM
3111 Biomedicine
3112 Neurosciences
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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