The YS mutation enhances both the sensitivity of RyR1 to activators (e.g. DHPR, caffeine, 4-chloro-m-cresol) and the temperature-dependence of RyR1 Ca2+ leak, alterations that underlie the MH susceptibility and exertional heat stroke phenotypes of these mice (Chelu et al., 2006; Durham et al., 2008; Lanner et al., 2012). The gene discussed is RYR1; the disease is Heat Stroke.