Mouse mtDNA mutant model of Leber hereditary optic neuropathy.
Proc Natl Acad Sci U S A
; 109(49): 20065-70, 2012 Dec 04.
Article
en En
| MEDLINE
| ID: mdl-23129651
ABSTRACT
An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Retina
/
ADN Mitocondrial
/
Estrés Oxidativo
/
Atrofia Óptica Hereditaria de Leber
/
Modelos Animales de Enfermedad
/
NADH Deshidrogenasa
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos