Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet.
Proc Natl Acad Sci U S A
; 108(49): 19678-82, 2011 Dec 06.
Article
en En
| MEDLINE
| ID: mdl-22106289
ABSTRACT
Deficiencies of subunits of the transcriptional regulatory complex Mediator generally result in embryonic lethality, precluding study of its physiological function. Here we describe a missense mutation in Med30 causing progressive cardiomyopathy in homozygous mice that, although viable during lactation, show precipitous lethality 2-3 wk after weaning. Expression profiling reveals pleiotropic changes in transcription of cardiac genes required for oxidative phosphorylation and mitochondrial integrity. Weaning mice to a ketogenic diet extends viability to 8.5 wk. Thus, we establish a mechanistic connection between Mediator and induction of a metabolic program for oxidative phosphorylation and fatty acid oxidation, in which lethal cardiomyopathy is mitigated by dietary intervention.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Miopatías Mitocondriales
/
Mutación Missense
/
Dieta Cetogénica
/
Complejo Mediador
/
Cardiomiopatías
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos