title: Accumulation of pathogenic DeltamtDNA induced deafness but not diabetic phenotypes in mito-mice.
abstract: Mito-mice carrying various proportions of deletion mutant mtDNA (DeltamtDNA) were generated by introduction of the DeltamtDNA from cultured cells into fertilized eggs of C57BL/6J (B6) strain mice. Great advantages of mito-mice are that they share exactly the same nuclear-genome background, and that their genetic variations are restricted to proportions of pathogenic DeltamtDNA. Since accumulation of DeltamtDNA to more than 75% induced respiration defects, the disease phenotypes observed exclusively in mito-mice carrying more than 75% DeltamtDNA should be due to accumulated DeltamtDNA. In this study, we focused on the expressions of hearing loss and diabetic phenotypes, since these common age-associated abnormalities have sometimes been reported to be inherited maternally and to be associated with pathogenic mutant mtDNAs. The results showed that accumulation of exogenously introduced DeltamtDNA was responsible for hearing loss, but not for expression of diabetic phenotypes in mito-mice.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8572, Japan;.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakada
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Sato
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sone
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kasahara
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015139:Blotting, Southern; D002467:Cell Nucleus / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D028361:Mitochondrial Diseases / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012119:Respiration; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial; D007328:Insulin; D011451:Prostaglandin-Endoperoxide Synthases