Canine MPV17 truncation without clinical manifestations
Hänninen, Reetta L. (Helsingin yliopisto. Department of Veterinary Biosciences)
Ahonen, Saija (Helsingin yliopisto. Department of Veterinary Biosciences)
Márquez Martínez, Mercedes (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Myöhänen, Maarit J. (Helsingin yliopisto)
Hytönen, Marjo K. (Helsingin yliopisto. Department of Veterinary Biosciences)
Lohi, Hannes (Helsingin yliopisto. Department of Veterinary Biosciences)

Fecha:	2015
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Dog ; Mtdna ; MPV17
Publicado en:	Biology open, Vol. 4 (2015) , p. 1253-1258, ISSN 2046-6390

DOI: 10.1242/bio.013870
PMID: 26353863

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