| Autor: |
Agostino A; Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, Istituto Nazionale Neurologico C. Besta-IRCCS, Milano, Italy., Invernizzi F, Tiveron C, Fagiolari G, Prelle A, Lamantea E, Giavazzi A, Battaglia G, Tatangelo L, Tiranti V, Zeviani M |
| Jazyk: |
angličtina |
| Zdroj: |
Human molecular genetics [Hum Mol Genet] 2003 Feb 15; Vol. 12 (4), pp. 399-413. |
| DOI: |
10.1093/hmg/ddg038 |
| Abstrakt: |
We report here the creation of a constitutive knockout mouse for SURF1, a gene encoding one of the assembly proteins involved in the formation of cytochrome c oxidase (COX). Loss-of-function mutations of SURF1 cause Leigh syndrome associated with an isolated and generalized COX deficiency in humans. The murine phenotype is characterized by the following hallmarks: (1) high post-implantation embryonic lethality, affecting approximately 90% of the Surf1(-/-) individuals; (2) early-onset mortality of post-natal individuals; (3) highly significant deficit in muscle strength and motor performance; (4) profound and isolated defect of COX activity in skeletal muscle and liver, and, to a lesser extent, heart and brain; (5) morphological abnormalities of skeletal muscle, characterized by reduced histochemical reaction to COX and mitochondrial proliferation; (6) no obvious abnormalities in brain morphology, reflecting the virtual absence of overt neurological symptoms. These results indicate a function for murine Surf1 protein (Surf1p) specifically related to COX and recapitulate, at least in part, the human phenotype. This is the first mammalian model for a nuclear disease gene of a human mitochondrial disorder. Our model constitutes a useful tool to investigate the function of Surf1p, help understand the pathogenesis of Surf1p deficiency in vivo, and evaluate the efficacy of treatment. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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