Phenotypes Associated with This Genotype

Genotype
MGI:4881413

• Allelic Composition: Ryr1^tm1.1Dhm/Ryr1⁺
• Genetic Background: involves: 129S2/SvPasCrl * 129S6/SvEvTac

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

Kyphosis, hindlimb paresis and myofiber abnormalities in Ryr1^tm1.1Dhm/Ryr1⁺ mice

muscle

abnormal muscle fiber morphology ( J:155825 )

• myofibers undergo a transition from small, compacted areas resembling minicores in younger mice to nemaline-rod like inclusions in adults

• type 2 (fast) myofibers exhibit gross structural defects in myofibrillar organization; myofibrils vary greatly in thickness and there are numerous sites of splitting and thinning

• type 1 fiber hypotrophy/atrophy is detected in muscle fibers as early as 6 weeks of age

abnormal sarcomere morphology ( J:155825 )

• spatial disruption of sarcomeric and myofibrillar arrangement of myofibers due to minicore/core lesions

• type 2 myofibrils exhibit sarcomeric shortening, insertion of an additional sarcomere, and loss of sarcomeric register

abnormal Z line morphology ( J:155825 )

• core lesions show Z-line streaming and focal loss of a Z-disk

abnormal skeletal muscle fiber morphology ( J:155825 )

• skeletal muscle exhibits increased endomysial spacing and mild fibrosis

• mutant soleus fibers exhibit minicores (discrete foci of oxidative enzyme depletion) at 12 months of age; by 20 months of age, larger areas of oxidative enzyme depletion, consistent with cores, are seen in type 1 fibers

• intermyofibrillar spaces are reduced and mitochondria and sarcoplasmic reticulum are absent from core lesion areas

decreased skeletal muscle fiber diameter ( J:155825 )

• at 18 months of age, type I and type 2 fibers have reduced diameters, suggesting general fiber atrophy

increased variability of skeletal muscle fiber size ( J:155825 )

impaired muscle contractility ( J:155825 )

• fast-twitch and slow-twitch muscles exhibit a 28-34% lower force during a single twitch and submaximal titanic contractions at 2 months of age

• about 37% decrease in peak twitch force and maximal twitch rate of contraction in muscles

muscle weakness ( J:155825 )

• mobility impairment is first seen as weakness of hind limbs at around 6 months of age

myopathy ( J:155825 )

• heterozygotes exhibit slowly progressive congenital myopathy, however show no evidence of muscle wasting or skeletal muscle degeneration

respiratory system

respiratory distress ( J:155825 )

• mutants start to breathe regularly 15-20 min after birth compared to 5-7 min for wild-type mice

skeleton

kyphosis ( J:155825 )

• heterozygotes develop dorsal kyphosis in the cervicothoracic region with age, most likely due to overuse of the forelimbs for locomotion

growth/size/body

decreased body weight ( J:155825 )

• average body weight is about 15% lower than in wild-type

behavior/neurological

abnormal locomotor behavior ( J:155825 )

• 80% of heterozygotes show varying degrees of motor dysfunction by 10 months of age

hindlimb paralysis ( J:155825 )

• by 12 months of age, 14% of mutants exhibit complete hind limb paralysis

homeostasis/metabolism

cyanosis ( J:155825 )

• mutants are flaccid and cyanotic during the first minutes after delivery

adipose tissue

decreased total body fat amount ( J:155825 )

• very low fat deposits

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital myopathy 1A		DOID:3529	OMIM:117000	J:155825