Phenotypes associated with this allele

• Allele Symbol: Sgcd^tm1Mcn
• Allele Name: targeted mutation 1, Elizabeth M McNally
• Allele ID: MGI:2180193
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sgcd^tm1Mcn/Sgcd^tm1Mcn	B6.129-Sgcd^tm1Mcn/J	MGI:5911876
hm2	Sgcd^tm1Mcn/Sgcd^tm1Mcn	involves: 129S1/Sv * 129T2/SvEmsJ * 129X1/SvJ	MGI:3618527

Genotype
MGI:5911876

hm1

• Allelic Composition: Sgcd^tm1Mcn/Sgcd^tm1Mcn
• Genetic Background: B6.129-Sgcd^tm1Mcn/J

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

muscle

cardiac muscle degeneration ( J:234761 )

• cardiac cell degeneration

cardiac muscle necrosis ( J:234761 )

abnormal skeletal muscle morphology ( J:250485 )

• accumulation of fat infiltrates in the muscle; fat infiltrates are more abundant in gastrocnemius and diaphragm muscles than in quadriceps and tibialis anterior muscles and marker analysis suggests that fat droplets are mostly white adipose tissue

skeletal muscle fibrosis ( J:250485 )

• muscles contain extensive fibrotic infiltrates, with the diaphragm most affected

• females show a significant increase in quadriceps and tibialis anterior muscle fibrosis

dystrophic muscle ( J:250485 )

• muscles show a shift towards smaller muscle fibers, increased expression of regeneration markers, indicating regenerative fibers, an accumulation of fat infiltrates in the muscle, and impaired muscle function

abnormal muscle physiology ( J:250485 )

• muscle function is impaired and declines over time

• the tibialis anterior muscle generates a lower specific force over a wide range of stimulation intensities (10-180 Hz)

• muscles generate a lower specific force than muscles from Sgca^tm2Kcam homozygotes

• tibialis anterior muscles repetitively stimulated at 120 Hz and stretched to 110% of their resting length show a 10-15% drop in isometric force compared to wild-type mice

dilated cardiomyopathy ( J:234761 )

• 14 week old mice develop signs of mild cardiomyopathy with patchy areas of fibrosis and necrosis

decreased cardiac muscle contractility ( J:234761 )

• heart function is reduced with mice showing reduced fractional shortening

behavior/neurological

decreased grip strength ( J:250485 )

• mice show a decrease in the normalized grip strength when male and female data are combined

• males hang for a shorter time period than wild-type mice in the two and four limb hanging tests

• performance in the two limb hanging test deteriorates over time

• however, no decline in performance in the four limb hanging test over time is seen

cardiovascular system

cardiac muscle degeneration ( J:234761 )

• cardiac cell degeneration

cardiac muscle necrosis ( J:234761 )

cardiac fibrosis ( J:234761 , J:250485 )

• hearts show an increase in Col1a1 expression and hearts from males contain higher collagen levels than females, indicating cardiac fibrosis (J:250485)

dilated cardiomyopathy ( J:234761 )

• 14 week old mice develop signs of mild cardiomyopathy with patchy areas of fibrosis and necrosis

decreased cardiac muscle contractility ( J:234761 )

• heart function is reduced with mice showing reduced fractional shortening

homeostasis/metabolism

increased circulating creatine kinase level ( J:250485 )

respiratory system

decreased pulmonary respiratory rate ( J:250485 )

• mice show lower respiration rates at 15 and 34 weeks of age

• however, respiration rate is higher than in Sgca^tm2Kcam homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2F		DOID:0110280	OMIM:601287	J:250485
dilated cardiomyopathy 1L		DOID:0110436	OMIM:606685	J:234761

Genotype
MGI:3618527

hm2

• Allelic Composition: Sgcd^tm1Mcn/Sgcd^tm1Mcn
• Genetic Background: involves: 129S1/Sv * 129T2/SvEmsJ * 129X1/SvJ

mortality/aging

premature death ( J:76730 )

• beginning at 8 weeks of age, begin to die suddenly

• premature mortality is also noted at 12, 16, and 28 weeks of age, with a 50% survival rate at 28 weeks of age

muscle

dystrophic muscle ( J:76730 )

• all skeletal muscles show dystrophic changes

• regional degeneration and regeneration of muscle fibers is common and accompanied by an inflammatory infiltrate

muscle degeneration ( J:76730 )

• skeletal and cardiac muscle degeneration

abnormal muscle physiology ( J:76730 )

• muscles exhibit pronounced Evans blue dye uptake, indicating alterations in membrane permeability of muscles

cardiomyopathy ( J:76730 )

• beginning at 12 weeks of age, observe signs of cardiac muscle degeneration as indicated by areas of cell death and inflammatory infiltrate

abnormal muscle contractility ( J:76730 )

• show a 42% drop in force generation over a five eccentric contraction protocol, however twich and tetanic force generation is normal

cardiovascular system

perivascular fibrosis ( J:76730 )

• frequent occurrence of perivascular fibrosis

cardiomyopathy ( J:76730 )

• beginning at 12 weeks of age, observe signs of cardiac muscle degeneration as indicated by areas of cell death and inflammatory infiltrate

homeostasis/metabolism

increased circulating creatine kinase level ( J:76730 )

• elevation in serum creatine kinase levels

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2F		DOID:0110280	OMIM:601287	J:76730
dilated cardiomyopathy 1L		DOID:0110436	OMIM:606685	J:76730