Phenotypes associated with this allele

• Allele Symbol: Sgcg^tm1Oza
• Allele Name: targeted mutation 1, Eijiro Ozawa
• Allele ID: MGI:3609567
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sgcg^tm1Oza/Sgcg^tm1Oza	involves: 129S4/SvJae * C57BL/6	MGI:3630163

Genotype
MGI:3630163

hm1

• Allelic Composition: Sgcg^tm1Oza/Sgcg^tm1Oza
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

mortality/aging

premature death ( J:102780 )

• most homozygotes (10 of 11) survive longer than 1 year of age with no evidence of stunted growth

• only one male homozygote (1 of 11) emaciated and died at 13 months while another male died at 20.5 months without any adumbration; the remaining 9 survived up to 2 years

muscle

myocardium necrosis ( J:102780 )

• 4 of 6 homozygotes at 8-14 weeks, 3 of 8 at 23-28 weeks, and 5 of 5 at 32-57 weeks of age display cardiac muscle cell necrosis with mononuclear cell infiltration and fibrosis either in the epicardial or endocardial regions, with marked variation in the location and extent of lesions

skeletal muscle necrosis ( J:102780 )

• at >10 weeks of age, all dissected skeletal muscles except the facial muscles appear pale, with white longitudinal stripes of various widths; necrotic muscle fibers are detected under the white stripes on H & E staining

• extensive muscle fiber necrosis and regeneration are observed at 7-17 weeks of age

abnormal tibialis anterior morphology ( J:102780 )

• at 32 weeks of age, the size of mutant TA muscle is increased to ~1.5-fold that of wild-type; the mutant TA appears pale, with longitudinal stripes at the left edge of the muscle

increased skeletal muscle fiber size ( J:102780 )

• at >12 weeks of age, homozygotes exhibit progressive hypertrophy of the limb, shoulder, and pelvic girdle muscles, associated with an increase in the number of slender muscle fibers, most of which have centrally placed nuclei (i.e. regenerating fibers)

abnormal diaphragm morphology ( J:102780 )

• homozygotes display muscle fiber necrosis in the diaphragm at 2 weeks after birth

increased skeletal muscle mass ( J:102780 )

• at 23 weeks of age, homozygotes of both sexes display significantly higher carcass weights relative to wild-type mice, indicating increased skeletal muscle mass

• however, no significant differences in whole body weights or other organ/body part weights are observed

skeletal muscle hypertrophy ( J:102780 )

• at >12 weeks of age, homozygotes exhibit generalized progressive hypertrophy of the limb, shoulder, and pelvic girdle muscles

skeletal muscle interstitial fibrosis ( J:102780 )

• skeletal muscle interstitial fibrosis is prevalent in the gastrocnemius, soleus, and tibialis posterior muscles

dystrophic muscle ( J:102780 )

• homozygotes display progressive dystrophic muscle changes, including significant variation in fiber size, necrotic and regenerative processes, and connective tissue proliferation, albeit small

• notably, fibrous and fat tissue replacement of muscle fibers appear at >30 weeks of age

• dystrophic changes are prevalent in the gastrocnemius, soleus, and tibialis posterior muscles, while muscle hypertrophy with replacement by regenerative muscle fibers is prevalent in the tibialis anterior, extensor digitorum longus, and peroneus longus and peroneus brevis muscles

muscle degeneration ( J:102780 )

• at 7 weeks of age, vital EBD staining reveals significant muscle fiber degeneration of variable extent in most skeletal muscles concomitant with highest CK activity

• however, skeletal muscle fiber degeneration tapers with age (>20 weeks of age)

abnormal muscle regeneration ( J:102780 )

• at >12 weeks of age, skeletal muscle hypertrophy is apparently due to an increase in the number of regenerating fibers following degeneration and not due to fat and fibrous tissue proliferation

progressive muscle weakness ( J:102780 )

• 20% of homozygotes under 22 weeks of age fall from a vertical wire mesh between 3 and 10 min while 54.1% of homozygotes at 22 weeks of age or over fall within 3 min, and 35.1% fall between 3 and 10 min; in contrast, all age-matched wild-type mice are able to hold on for longer than 10 min

cardiovascular system

myocardium necrosis ( J:102780 )

• 4 of 6 homozygotes at 8-14 weeks, 3 of 8 at 23-28 weeks, and 5 of 5 at 32-57 weeks of age display cardiac muscle cell necrosis with mononuclear cell infiltration and fibrosis either in the epicardial or endocardial regions, with marked variation in the location and extent of lesions

cardiac fibrosis ( J:102780 )

• homozygotes that die at <2 years of age (2 of 11) display muscle fiber necrosis and cardiac fibrosis

• homozygotes that survive up to 2 years show progressive focal cardiac muscle fiber fibrosis after 33 weeks of age; by 32-57 weeks, all homozygotes exhibit cardiac fibrosis either in the epicardial or endocardial regions

homeostasis/metabolism

increased circulating creatine kinase level ( J:102780 )

• homozygotes show a 4-fold elevation of serum creatine kinase activities at 3-4 weeks of age, 100-fold at 8-10 weeks of age, and 10-fold in excess of 20 weeks relative to age-matched wild-type mice

cellular

myocardium necrosis ( J:102780 )

• 4 of 6 homozygotes at 8-14 weeks, 3 of 8 at 23-28 weeks, and 5 of 5 at 32-57 weeks of age display cardiac muscle cell necrosis with mononuclear cell infiltration and fibrosis either in the epicardial or endocardial regions, with marked variation in the location and extent of lesions

skeletal muscle necrosis ( J:102780 )

• at >10 weeks of age, all dissected skeletal muscles except the facial muscles appear pale, with white longitudinal stripes of various widths; necrotic muscle fibers are detected under the white stripes on H & E staining

• extensive muscle fiber necrosis and regeneration are observed at 7-17 weeks of age

limbs/digits/tail

abnormal tibialis anterior morphology ( J:102780 )

• at 32 weeks of age, the size of mutant TA muscle is increased to ~1.5-fold that of wild-type; the mutant TA appears pale, with longitudinal stripes at the left edge of the muscle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2C		DOID:0110277	OMIM:253700	J:102780