Phenotypes associated with this allele

• Allele Symbol: Ryr1^em1Tmur
• Allele Name: endonuclease-mediated mutation 1, Takashi Murayama
• Allele ID: MGI:7258399
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ryr1^em1Tmur/Ryr1^em1Tmur	Not Specified	MGI:7260234
ht2	Ryr1^em1Tmur/Ryr1^+	Not Specified	MGI:7260233

Genotype
MGI:7260234

hm1

• Allelic Composition: Ryr1^em1Tmur/Ryr1^em1Tmur
• Genetic Background: Not Specified

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:322211 )

• mice die in late embryonic stage

Genotype
MGI:7260233

ht2

• Allelic Composition: Ryr1^em1Tmur/Ryr1⁺
• Genetic Background: Not Specified

homeostasis/metabolism

abnormal body temperature homeostasis ( J:322211 )

• mice anesthetized using intravenous anesthetics and exposed to environmental heat stress (35 degrees Celsius) exhibit heat stroke and die

• pretreatment of mice exposed to environmental heat stress with Cpd1 slows the rate of temperature rise but maximum rectal temperature does not change and none of the mice survive 120 min of heat stress, although time to death is prolonged

• mice exposed to environmental heat stress and then treated with Cpd1 when rectal temperature reached 39 degrees Celsius rescues most mice from heat stroke at 10 mg/kg Cpd1 and partially rescues at 3 mg/kg; treatment with Cpd1 when temperature reached 38 degrees Celsius rescues most mice from heat stroke

increased physiological sensitivity to xenobiotic ( J:322211 )

• isolated single flexor digitorum brevis muscle cells treated with halothane up to 0.1% or with isoflurane show an increase in intracellular calcium concentration that is not seen in wild-type cells

• isolated soleus muscles exhibit dose-dependent contracture during exposure to caffeine compared to wild-type muscles which show minimal contracture

increased susceptibility to malignant hyperthermia ( J:322211 )

• nearly 80% of mice anesthetized by isoflurane rapidly increase their rectal temperature to over 40 degrees Celsius, exhibit muscle rigidity, and die within 90 minutes from start of exposure compared to wild-type mice which show no elevation in rectal temperature

• in the remaining 20% of mice, exposure to isoflurane causes an increase in rectal temperature but does not exceed 39 degrees Celsius

• more males (90%) succumb to isoflurane than females (65%)

• males pretreated with 10 mg/kg, but not 3 mg/kg, of Cpd1 sodium salt (a derivative of oxolinic acid that inhibits the RyR1 channel) before isoflurane challenge show prevention of rise in rectal temperature and all mice survive

• mice anesthetized with isoflurane and administered Cpd1 when rectal temperature reached 39 degrees Celsius show a decrease in body temperature and 60% of mice treated with 3mg/kg and 100% of mice treated with 10mg/kg of Cpd1 survive

muscle

abnormal muscle physiology ( J:322211 )

• isolated single flexor digitorum brevis muscle cells treated with halothane up to 0.1% or with isoflurane show an increase in intracellular calcium concentration that is not seen in wild-type cells

• pretreatment of flexor digitorum brevis muscle cells with a Cpd1 sodium salt (a derivative of oxolinic acid that inhibits the RyR1 channel) reduces resting intracellular calcium concentration and completely abolishes halothane-induced or isoflurane-induced increases in intracellular calcium

• isolated soleus muscles exhibit dose-dependent contracture during exposure to caffeine compared to wild-type muscles which show minimal contracture

• pretreatment with Cpd1 decreases caffeine-induced contracture tension of soleus muscle basal tension of soleus muscle at 42 degrees Celsius is increased compared to in wild-type muscle and pre-treatment with Cpd1 reduces the heat-induced contracture

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant hyperthermia		DOID:8545	OMIM:PS145600	J:322211