Phenotypes associated with this allele

• Allele Symbol: Large1^myd
• Allele Name: myodystrophy
• Allele ID: MGI:1856965
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Large1^myd/Large1^myd	B6C3Fe a/a-Large1^myd/J	MGI:3607259
hm2	Large1^myd/Large1^myd	B6.Cg-Large1^myd/Pjn	MGI:3605230
hm3	Large1^myd/Large1^myd	MYD/Le-Os +/+ Large^myd/J	MGI:2175098
ht4	Large1^myd/Large1^+	B6C3Fe a/a-Large1^myd/J	MGI:3607261
cx5	Dysf^im/Dysf^+ Large1^myd/Large1^myd	involves: C57BL/6 * SJL/J	MGI:5700215
cx6	Dysf^im/Dysf^im Large1^myd/Large1^myd	involves: C57BL/6 * SJL/J	MGI:5700216

Genotype
MGI:3607259

hm1

• Allelic Composition: Large1^myd/Large1^myd
• Genetic Background: B6C3Fe a/a-Large1^myd/J

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

muscle

abnormal myocardium layer morphology ( J:169951 )

• focal interstitial myocardial collagen deposition is seen at 10 months of age, indicating cardiac remodeling that occurs following myocardial damage

abnormal myocardial fiber morphology ( J:169951 )

• mutants exhibit focal patches of cardiac myocyte membrane damage

myositis ( J:27793 )

• accompanies skeletal muscle fiber necrosis

abnormal skeletal muscle fiber morphology ( J:27793 )

skeletal muscle fiber necrosis ( J:27793 )

• in addition to foci of 20-50 necrotic fibers, individual or smaller groups of necrotic fibers are also seen

increased variability of skeletal muscle fiber size ( J:27793 )

• both fast and slow muscle fiber types show increased size variation

centrally nucleated skeletal muscle fibers ( J:27793 )

skeletal muscle fiber degeneration ( J:27793 )

• many degenerating and regenerating fibers

• foci of degeneration are typically large, irregularly shaped and involve 20-50 necrotic fibers

calcified muscle ( J:27793 )

• dystrophic calcification is seen ion areas of skeletal muscle necrosis

dystrophic muscle ( J:144746 )

immune system

myositis ( J:27793 )

• accompanies skeletal muscle fiber necrosis

hearing/vestibular/ear

abnormal auditory brainstem response waveform shape ( J:27793 )

• prolonged I-IV interpeak latencies

• decreased wave IV amplitude

• mean wave IV threshold increased

sensorineural hearing loss ( J:27793 )

cardiovascular system

abnormal myocardium layer morphology ( J:169951 )

• focal interstitial myocardial collagen deposition is seen at 10 months of age, indicating cardiac remodeling that occurs following myocardial damage

abnormal myocardial fiber morphology ( J:169951 )

• mutants exhibit focal patches of cardiac myocyte membrane damage

homeostasis/metabolism

increased circulating creatine kinase level ( J:27793 )

• affected animals have an elevated serum CK range compared to controls

abnormal enzyme/coenzyme activity ( J:144746 )

• mice exhibit hypoglycosylation of almost all alpha-dystroglycan compared to in wild-type mice

• laminin-binding activity of alpha-dystroglycan is less than 5% of normal

behavior/neurological

limb grasping ( J:27793 )

• homozygous mice tightly adduct the hindlimbs and curl toes when suspended by the tail

abnormal gait ( J:27793 )

• variable severity at 3 weeks of age; some exhibit gait abnormalities and others could not be identified by this observation

growth/size/body

decreased body size ( J:27793 )

• variable severity at 3 weeks of age; some are clearly smaller and others could not be identified by size

cellular

skeletal muscle fiber necrosis ( J:27793 )

• in addition to foci of 20-50 necrotic fibers, individual or smaller groups of necrotic fibers are also seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
facioscapulohumeral muscular dystrophy		DOID:11727		J:27793

Genotype
MGI:3605230

hm2

• Allelic Composition: Large1^myd/Large1^myd
• Genetic Background: B6.Cg-Large1^myd/Pjn

vision/eye

abnormal retina layer morphology ( J:100214 )

thin retina outer nuclear layer ( J:100214 )

• almost 50% thinner than in controls

disorganized retina outer plexiform layer ( J:100214 )

• layer is disorganized with a reduction in synaptic complexes

• mitochondria are swollen with severe disruption of cristae

• exhibits extracelluelar edema

• layer is thinner than in control littermates

abnormal eye electrophysiology ( J:100214 )

• amplitude of b-wave responses is reduced and delayed at all flash intensities in 2 month old mice

• larger negative polarity a-wave in response to intermediate flash intensities in 2 month old mice

• maximum amplitude of a-wave reduced in response to highest flash intensities in 2 month old mice

muscle

abnormal myocardium layer morphology ( J:100214 )

• myocardium exhibits mild to moderate areas of cardiomyocyte degeneration with mycytolysis, necrosis and interstitial fibrosis in 5 month old mice

• lesions observed in the left and right atria and ventricles

dilated cardiomyopathy ( J:100214 )

• adult onset

abnormal soleus morphology ( J:100214 )

• occasional signs of fiber-type grouping in 6 month old mice

abnormal diaphragm morphology ( J:100214 )

• exhibits prominent interstial fibrosis with extensive degeneration and regeneration of myofibers at 1.5 months of age

• by 4 months diaphragm exhibits necrosis and fatty infiltration

cardiovascular system

abnormal myocardium layer morphology ( J:100214 )

• myocardium exhibits mild to moderate areas of cardiomyocyte degeneration with mycytolysis, necrosis and interstitial fibrosis in 5 month old mice

• lesions observed in the left and right atria and ventricles

dilated cardiomyopathy ( J:100214 )

• adult onset

limbs/digits/tail

abnormal soleus morphology ( J:100214 )

• occasional signs of fiber-type grouping in 6 month old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
muscular dystrophy-dystroglycanopathy type B1		DOID:0050588	OMIM:613155	J:100214

Genotype
MGI:2175098

hm3

• Allelic Composition: Large1^myd/Large1^myd
• Genetic Background: MYD/Le-Os +/+ Large^myd/J

mortality/aging

premature death ( J:5670 )

• average life span 17.25 weeks, range 5-39 weeks

behavior/neurological

limb grasping ( J:5670 )

• involves hind limbs

• adduction of hind legs, flexion of the knee, ankles and toes

• severe contraction of hind limbs sometimes by 3-4 months of age

abnormal gait ( J:5670 )

• hind limbs held close to the body producing a short, shuffling gait

• hind limbs never extended and dragged

muscle

abnormal muscle morphology ( J:5670 )

abnormal skeletal muscle fiber morphology ( J:5670 )

• variable fiber size

• loss of striation

• central migration of nuclei

• nuclear "rowing"

calcified muscle ( J:12034 )

• elevated calcium levels in skeletal muscles, particularly the diaphragm

• heart not affected

dystrophic muscle ( J:5670 )

muscle degeneration ( J:5670 )

abnormal muscle physiology ( J:5670 )

myositis ( J:5670 )

• mononuclear cell infiltration of areas surrounding degenerating fibers

myopathy ( J:5670 )

• diffuse and progressive myopathy

• widely distributed focal lesions in skeletal muscles as early as 16 days of age

nervous system

absent Schwann cells ( J:5974 )

• usually unmyelinated nerves lack Schwann cells but sometimes Schwann cells present but lacking myelin

abnormal spinal nerve morphology ( J:5974 )

• areas completely deficient in myelin

• not every root is affected

• observed in dorsal roots T13 to S1 and Ventral roots L1 to S1 (except L5)

• L3 and L4 ventral roots most severely affected

abnormal myelination ( J:5974 )

• areas where nerves are completely deficient in myelin

growth/size/body

abnormal tongue morphology ( J:5670 )

• musculature of tongue not affected until later

• subepithelial fibrosis in tongues of older mice

decreased body weight ( J:5670 )

• organ weights reduced comparably with reduced body weigh

postnatal growth retardation ( J:5670 )

• very severe at weaning

• growth improved after weaning but mice always small

skeleton

kyphosis ( J:5670 )

• thoracic kyphosis by 6-8 weeks of age

• becoming progressively worse with age

abnormal bone structure ( J:12034 )

• thinning of all bones examined

reproductive system

reduced fertility ( J:5670 )

• although not sterile, reproduction is very poor

immune system

myositis ( J:5670 )

• mononuclear cell infiltration of areas surrounding degenerating fibers

digestive/alimentary system

abnormal tongue morphology ( J:5670 )

• musculature of tongue not affected until later

• subepithelial fibrosis in tongues of older mice

craniofacial

abnormal tongue morphology ( J:5670 )

• musculature of tongue not affected until later

• subepithelial fibrosis in tongues of older mice

Genotype
MGI:3607261

ht4

• Allelic Composition: Large1^myd/Large1⁺
• Genetic Background: B6C3Fe a/a-Large1^myd/J

behavior/neurological

limb grasping ( J:27793 )

• some aging animals exhibit atypical hindlimb posture and movements when lifted by the tail

Genotype
MGI:5700215

cx5

• Allelic Composition: Dysf^im/Dysf⁺; Large1^myd/Large1^myd
• Genetic Background: involves: C57BL/6 * SJL/J

muscle

myositis ( J:221523 )

• macrophage infiltration is increased in skeletal muscle

abnormal skeletal muscle fiber morphology ( J:221523 )

• albumin-positive myofibers are increased in skeletal muscle indicating deterioration of the myofiber membrane fragility

skeletal muscle fiber necrosis ( J:221523 )

increased variability of skeletal muscle fiber size ( J:221523 )

• some mice show variation in fiber size and connective tissue infiltration

centrally nucleated skeletal muscle fibers ( J:221523 )

skeletal muscle fiber degeneration ( J:221523 )

• mice show necrotic and centrally located nucleated myofibers, indicating frequent cycles of muscle degeneration and regeneration

dystrophic muscle ( J:221523 )

• some mice show advanced muscular dystrophic changes such as variation in fiber size and connective tissue infiltration

immune system

myositis ( J:221523 )

• macrophage infiltration is increased in skeletal muscle

cellular

skeletal muscle fiber necrosis ( J:221523 )

Genotype
MGI:5700216

cx6

• Allelic Composition: Dysf^im/Dysf^im; Large1^myd/Large1^myd
• Genetic Background: involves: C57BL/6 * SJL/J

muscle

myositis ( J:221523 )

• macrophage infiltration is increased in skeletal muscle

abnormal skeletal muscle fiber morphology ( J:221523 )

• albumin-positive myofibers are increased in skeletal muscle indicating deterioration of the myofiber membrane fragility

increased variability of skeletal muscle fiber size ( J:221523 )

dystrophic muscle ( J:221523 )

• mice show severe muscle pathology, including marked variation in fiber size and large areas with connective tissue infiltration

immune system

myositis ( J:221523 )

• macrophage infiltration is increased in skeletal muscle