SCID mice containing muscle with human mitochondrial DNA mutations - An animal model for mitochondrial DNA defects

• Tipo: Artigo em Revista Científica Internacional
• Data: 1998

Autores

Clark, KM (Autor) Outra; Watt, DJ (Autor) Outra; Lightowlers, RN (Autor) Outra; Johnson, MA (Autor) Outra; Relvas, JB (Autor) Outra; Taanman, JW (Autor) Outra; Turnbull, DM (Autor) Outra

Revista

Título: Journal of Clinical Investigation

Vol. 102

Páginas: 2090-2095

ISSN: 0021-9738

Editora: American Society for Clinical Investigation

Indexação

ISI Web of Knowledge - 6 Citações

Scopus - 8 Citações

Outras Informações

ID Authenticus: P-00F-NZ8

DOI: 10.1172/jci944

Abstract (EN): Defects of the mitochondrial genome are important causes of disease. Despite major advances in our investigation of patients, there is no effective therapy. Progress in this area is limited by the absence of any animal models in which we can evaluate treatment. To develop such a model we have injected human myoblasts into the tibialis anterior of SCID mice after inducing necrosis, After injection of normal human myoblasts, regenerating fibers expressed human P-spectrin, confirming they were derived from fusion of human myoblasts. The stability of the muscle fibers was inferred by demonstrating the formation of motor end plates on the regenerating fibers. In addition, we show the presence of human cytochrome c oxidase subunit II, which is encoded by the mitochondrial genome, in the regenerated fibers. After injection of human myoblasts containing either the A8344G or the T8993C heteroplasmic mitochondrial DNA mutations, human P-spectrin positive fibers were found to contain the mutation at a similar level to the injected myoblasts. These studies highlight the potential value of this model for the study of mitochondrial DNA defects.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6