Phenotypes Associated with This Genotype

Genotype
MGI:6515831

• Allelic Composition: Ryr1^tm3.1Alle/Ryr1^tm3.1Alle
• Genetic Background: involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:303297 )

• exposure to increased environmental temperature triggers fulminant heat stroke resulting in death, with a mean time to death of 17.9 minutes

premature death ( J:303297 )

♂ • in approximately the F6 generation, males frequently die at 3-8 weeks of age

♂ • some homozygous males housed with littermate heterozygotes or wild-type males die within 8 weeks and if housed only with homozygous littermates, they survive up to 22 weeks before spontaneous death

♂ • only 3 homozygous females die spontaneously within 18 months

homeostasis/metabolism

abnormal body temperature homeostasis ( J:303297 )

• exposure to increased environmental temperature triggers fulminant heat stroke resulting in death, with a mean time to death of 17.9 minutes and maximum temperature reached at 39.8 degrees C

increased physiological sensitivity to xenobiotic ( J:303297 )

• mice exposed to halothane exhibit a 3.6-fold and 1.6-fold elevation of intracellular calcium and sodium, respectively in vastus lateralis muscle

• mice exposed to isoflurane exhibit a 4.6-fold and 1.9-fold elevation of intracellular calcium and sodium, respectively in vastus lateralis muscle

• myotubes in vitro show increased sensitivity to halothane

increased susceptibility to malignant hyperthermia ( J:303297 )

• mice exhibit increased sensitivity to halothane, with a mean time to death of 18 minutes and their mean maximum temperature of 41 degrees C compared to 100% survival of wild-type mice with a mean ending temperature at 70 min of 37 degrees C

muscle

abnormal muscle physiology ( J:303297 )

• the normalized half-maximal effective concentration for intracellular calcium release in myotubes in response to KCl and caffeine are decreased

• in vivo quiescent muscle fibers of the vastus lateralis show increased intracellular calcium and sodium concentrations

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant hyperthermia		DOID:8545	OMIM:PS145600	J:303297