title: Cyclophilin D-dependent mitochondrial permeability transition is not involved in neurodegeneration in mnd2 mutant mice.
abstract: Parkinson's disease (PD) is a common neurodegenerative disorder. The motor neuron degeneration 2 mutant (mnd2) mouse exhibits loss of striatal neurons, muscle wasting, weight loss, and death within 40days of birth, and is considered to be a useful animal model of PD. mnd2 was identified as an autosomal recessive mutation in the HtrA2/Omi gene, which encodes a mitochondrial serine protease. Omi-deficient mitochondria are more sensitive to mitochondrial permeability transition (mPT), which raises the possibility that mPT plays a role in motor neurodegeneration in mnd2 mice. Given that cyclophilin D (CypD)-deficient mitochondria are resistant to mPT, we examined whether CypD-dependent mPT is involved in the pathogenesis of neurodegenerative disorders in mnd2 mice by generating CypD-deficient mnd2 mice. Brain mitochondria isolated from CypD-deficient mnd2 mice were more resistant to Ca(2+)-induced mPT than those of mnd2 mice. However, both mnd2 mice and CypD-deficient mnd2 mice showed similar survival periods and phenotypes, including the lack of weight gain, muscle wasting, and resting tremor. Our data suggest that CypD-dependent mPT does not play a major role in neurodegeneration in mnd2 mice.
authors.affiliation: Department of General Thoracic Surgery, Osaka University Medical School, Yamadaoka, Suita, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Ideguchi
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Meinoshin
authors.initials: M
authors.lastname: Okumura
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Tsujimoto
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism*; D000074923:High-Temperature Requirement A Serine Peptidase 2; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000235:genetics; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics; D010539:Permeability; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D024101:Mitochondrial Proteins; C000631446:PPIF protein, mouse; D012697:Serine Endopeptidases; D000074923:High-Temperature Requirement A Serine Peptidase 2; C000615915:Htra2 protein, mouse; D021983:Cyclophilins