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Publication
Sex-specific alterations in whole body energetics and voluntary activity in
heterozygous R163C malignant hyperthermia-susceptible mice.
Authors Rutkowsky JM, Knotts TA, Allen PD, Pessah IN, Ramsey JJ
Submitted By Submitted Externally on 3/9/2022
Status Published
Journal FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Year 2020
Date Published 6/1/2020
Volume : Pages 34 : 8721 - 8733
PubMed Reference 32367593
Abstract Malignant hyperthermia (MH) is characterized by induction of skeletal muscle
hyperthermia in response to a dysregulated increase in myoplasmic calcium.
Although altered energetics play a central role in MH, MH-susceptible humans and
mouse models are often described as having no phenotype until exposure to a
triggering agent. The purpose of this study was to determine the influence of
the R163C ryanodine receptor 1 mutation, a common MH mutation in humans, on
energy expenditure, and voluntary wheel running in mice. Energy expenditure was
measured by indirect respiration calorimetry in wild-type (WT) and heterozygous
R163C (HET) mice over a range of ambient temperatures. Energy expenditure
adjusted for body weight or lean mass was increased (P < .05) in male, but not
female, HET mice housed at 22°C or when housed at 28°C with a running wheel. In
female mice, voluntary wheel running was decreased (P < .05) in the HET vs WT
animals when analyzed across ambient temperatures. The thermoneutral zone was
also widened in both male and female HET mice. The results of the study show
that the R163C mutations alters energetics even at temperatures that do not
typically induce MH.




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