Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet

Krebs, Philippe; Fan, Weiwei; Chen, Yen-Hui; Tobita, Kimimasa; Downes, Michael R; Wood, Malcolm R; Sun, Lei; Li, Xiaohong; Xia, Yu; Ding, Ning; Spaeth, Jason M; Moresco, Eva Marie Y; Boyer, Thomas G; Lo, Cecilia Wen Ya; Yen, Jeffrey; Evans, Ronald M; Beutler, Bruce (2011). Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 108(49), pp. 19678-82. Washington, D.C.: National Academy of Sciences NAS 10.1073/pnas.1117835108

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Krebs, Philippe

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:18

Last Modified:

10 Apr 2014 19:50

Publisher DOI:

10.1073/pnas.1117835108

PubMed ID:

22106289

Web of Science ID:

000297683800053

URI:

https://boris.unibe.ch/id/eprint/5523 (FactScience: 210276)

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