Phenotypes associated with this allele

• Allele Symbol: Sgca^tm2Kcam
• Allele Name: targeted mutation 2, Kevin P Campbell
• Allele ID: MGI:3772334
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sgca^tm2Kcam/Sgca^tm2Kcam	B6.129S6-Sgca^tm2Kcam/J	MGI:7278768
hm2	Sgca^tm2Kcam/Sgca^tm2Kcam	either: (129S6/SvEvTac-Sgca^tm2Kcam) or (involves: 129S6/SvEvTac * C57BL/6J)	MGI:3772351
cn3	Sgca^tm2Kcam/Sgca^tm2Kcam Tg(Ckmm-cre)5Khn/0	either: (involves: 129S4/SvJae * 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6J * FVB)	MGI:3772354

Genotype
MGI:7278768

hm1

• Allelic Composition: Sgca^tm2Kcam/Sgca^tm2Kcam
• Genetic Background: B6.129S6-Sgca^tm2Kcam/J

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

muscle

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 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 higher specific force than muscles from Sgcd^tm1Mcn 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

behavior/neurological

decreased grip strength ( J:250485 )

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

• mice perform worse in the hanging tests than Sgcd^tm1Mcn homozygotes

• performance in the two limb hanging test and the four limb hanging test deteriorates over time

• however, no significant differences are seen in the rotarod test or balance beam test

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

• respiration rate is lower than in Sgcd^tm1Mcn homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2D		DOID:0110278	OMIM:608099	J:250485

Genotype
MGI:3772351

hm2

• Allelic Composition: Sgca^tm2Kcam/Sgca^tm2Kcam
• Genetic Background: either: (129S6/SvEvTac-Sgca^tm2Kcam) or (involves: 129S6/SvEvTac * C57BL/6J)

muscle

abnormal muscle fiber morphology ( J:130252 )

• skeletal muscle shows fiber size variation, fiber degeneration and regeneration, and centrally located nuclei, characteristic of muscular dystrophy

• phenotype is stated to be identical to that of Sgca^tm1Kcam homozygotes; however no data are presented

abnormal sarcolemma morphology ( J:130252 )

• membrane damage is exhibited in quadriceps muscles as shown by uptake of Evans blue dye into fibers between 3 and 12 months

increased muscle weight ( J:130252 )

calcified muscle ( J:130252 )

dystrophic muscle ( J:130252 )

• mice develop muscular dystrophy essentially identical to that show by Sgca^tm1Kcam homozygotes

abnormal muscle contractility ( J:130252 )

homeostasis/metabolism

increased circulating creatine kinase level ( J:130252 )

• at 10-12 weeks, mutants show significantly elevated basal levels of creatine kinase in the blood, relative to wild-type; exercise-induced mechanical stress of the sarcolemmal membrane resulted in a further 3-fold increase in creatine kinase in serum

Genotype
MGI:3772354

cn3

• Allelic Composition: Sgca^tm2Kcam/Sgca^tm2Kcam; Tg(Ckmm-cre)5Khn/0
• Genetic Background: either: (involves: 129S4/SvJae * 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6J * FVB)

muscle

muscle phenotype ( J:130252 )

N • conditional mutants fail to develop muscular dystrophy pathology; striated and cardiac muscle show expression of mutant alpha-sarcoglycan, as well as sarcospan

N • percentage of fibers with centrally located nuclei are normalized to levels of heterozygous non-transgenic controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:130252 )

N • serum creatine kinase levels are normalized