Phenotypes associated with this allele

• Allele Symbol: Ryr1^tm1Slh
• Allele Name: targeted mutation 1, Susan L Hamilton
• Allele ID: MGI:3619253
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ryr1^tm1Slh/Ryr1^tm1Slh	involves: 129S7/SvEvBrd * C57BL/6	MGI:3620043
ht2	Ryr1^tm1Slh/Ryr1^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3620044

Genotype
MGI:3620043

hm1

• Allelic Composition: Ryr1^tm1Slh/Ryr1^tm1Slh
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

mortality/aging

perinatal lethality, complete penetrance ( J:105738 )

• homozygotes are alive at E17.5 but die by P1

muscle

abnormal skeletal muscle morphology ( J:105738 )

• skeletal muscle is dysmorphic

abnormal skeletal muscle fiber morphology ( J:105738 )

• myofibrillar disorganization and internalized nuclei with atypical shapes are seen

increased variability of skeletal muscle fiber size ( J:105738 )

• an increased range of skeletal muscle fiber diameters is seen

abnormal muscle physiology ( J:105738 )

• electrically invoked and caffeine-induced Ca2+ release from sarcoplasmic reticulum vesicles is reduced in isolated myotubes; however, resting intracellular Ca2+ are not increased

• in isolated myotubes the magnitude of L-type Ca2+ currents and voltage-gated Ca2+ release are reduced and shifted towards more hyperpolarized potentials

homeostasis/metabolism

edema ( J:105738 )

• massive edema and subcutaneous blood effusions are present at E17.5

skeleton

abnormal rib morphology ( J:105738 )

• wavy caudal ribs

abnormal thoracic cage shape ( J:105738 )

• the rib cage is compressed longitudinally and enlarged dorsal-ventrally

kyphosis ( J:105738 )

• at E17.5

growth/size/body

omphalocele ( J:105738 )

• at E17.5

pectus excavatum ( J:105738 )

• pectus excavatus (sternum is pushed inward)

Genotype
MGI:3620044

ht2

• Allelic Composition: Ryr1^tm1Slh/Ryr1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

muscle

abnormal muscle physiology ( J:105738 )

• isolated muscle sarcoplasmic reticulum vesicles have a significant reduction in Ca2+ loading at 37 degrees C and voltage dependent Ca2+ release is shifted toward more negative voltages in isolate myotubes

abnormal muscle contractility ( J:105738 )

• the soleus muscle is more sensitive to caffeine-induced activation in an in vitro contracture test

• increasing the temperature to 41 degrees C for 15 min or less induces full body contractures with agonal breathing, rigid extremities, and arched backs

• isolated muscles display increased basal tension between 35-36 degrees C (43-44 degrees C for the diaphragm)

homeostasis/metabolism

increased circulating potassium level ( J:105738 )

• during heat induced contractures serum potassium and creatine kinase levels increase by 80% and 163% respectively compared to pre-heat challenge levels suggesting rhabdomyolysis has occurred, no such increase is seen in wild-type mice after heating

abnormal body temperature homeostasis ( J:105738 )

• after heat challenge (increased external temperature to 41 degrees C for less than 15 min) body temperature increases to 43.4 +/- 0.8 degrees C compared to 41.1 +/- 0.3 degrees C in wild-type mice

behavior/neurological

enhanced behavioral response to xenobiotic ( J:105738 )

• exposure to about 5.5 x 10^-5 ml/cm³ isoflurane induces a rapid onset of malignant hyperthermic response with full body contractures and increased core temperatures

• increasing the room temperature from less than 25 degrees C to 30 degrees C increases the penetrance of the malignant hyperthermic response

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant hyperthermia		DOID:8545	OMIM:PS145600	J:105738