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
Title: | Canine MPV17 truncation without clinical manifestations |
Author: | Hanninen, Reetta L.; Ahonen, Saija; Marquez, Merce; Myohanen, Maarit J.; Hytonen, Marjo K.; Lohi, Hannes |
Contributor organization: | Departments of Faculty of Veterinary Medicine Research Programs Unit Research Programme for Molecular Neurology Veterinary Biosciences Hannes Tapani Lohi / Principal Investigator |
Date: | 2015-10-15 |
Language: | eng |
Number of pages: | 6 |
Belongs to series: | Biology open |
ISSN: | 2046-6390 |
DOI: | https://doi.org/10.1242/bio.013870 |
URI: | http://hdl.handle.net/10138/159059 |
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. |
Subject: |
Dog
mtDNA MPV17 MITOCHONDRIAL-DNA DEPLETION HEPATOCEREBRAL FORM MTDNA DEPLETION LIVER-FAILURE GENE MPV17 MUTATION ENCODES PROTEIN DEFICIENCY METABOLISM 3111 Biomedicine 3112 Neurosciences |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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