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Publication
Loss of the melanocortin-4 receptor in mice causes dilated cardiomyopathy.
Authors Litt MJ, Okoye GD, Lark D, Cakir I, Moore C, Barber MC, Atkinson J, Fessel J,
Moslehi J, Cone RD
Submitted By Submitted Externally on 7/18/2018
Status Published
Journal eLife
Year 2017
Date Published 8/22/2017
Volume : Pages 6 : Not Specified
PubMed Reference 28829041
Abstract Haploinsufficiency of the melanocortin-4 receptor, the most common monogenetic
obesity syndrome in humans, is associated with a reduction in autonomic tone,
bradycardia, and incidence of obesity-associated hypertension. Thus, it has been
assumed that melanocortin obesity syndrome may be protective with respect to
obesity-associated cardiovascular disease. We show here that absence of the
melanocortin-4 receptor (MC4R) in mice causes dilated cardiomyopathy,
characterized by reduced contractility and increased left ventricular diameter.
This cardiomyopathy is independent of obesity as weight matched diet induced
obese mice do not display systolic dysfunction. Mc4r cardiomyopathy is
characterized by ultrastructural changes in mitochondrial morphology and
cardiomyocyte disorganization. Remarkably, testing of myocardial tissue from
Mc4r-/- mice exhibited increased ADP stimulated respiratory capacity. However,
this increase in respiration correlates with increased reactive oxygen species
production - a canonical mediator of tissue damage. Together this study
identifies MC4R deletion as a novel and potentially clinically important cause
of heart failure.




Strains
StrainDevelopment StatusCreation MethodOptions
C57BL/6-Mc4rtm1DhuPhenotyping ongoingknockout
View
B6.129S4-Mc4rtm1DhuPhenotyping ongoingknockout
View




Genes
SymbolDescription
Mc4rmelanocortin 4 receptor

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