Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   14-JUL-09 Species laboratory mouse   Donating Investigator Kevin Campbell,   University of Iowa

Description
Homozyous mice are viable and fertile. They develop severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. Severe dystrophic changes including necrosis, dystrophic calcification, fatty infiltration, central nucleation, fibrosis, atrophy and hypertrophy are detected in diaphragm and calf/thigh muscle. Some of these changes occur in 4-week-old animals and accumulate with age. At 20 weeks of age, several regions of focal myocardial necrosis have been observed; small areas of necrotic myocardiocytes may be observed as early as 9 weeks of age. At 30 weeks of age, large areas of fibrosis are detected. Sarcoglycan-sarcospan and dystroglycan complexes are disrupted in skeletal, cardiac, and smooth muscle membranes. Loss of the sarcoglycan-sarcospan complex in vascular smooth muscle results in vascular irregularities in heart, diaphragm, and kidneys. Vascular constrictions in skeletal muscle, cardiac muscle and kidneys is observed. Epsilon-sarcoglycan (SGCE) is also reduced in membrane preparations of striated and smooth muscle. The muscular dystrophy phenotype is reportedly more severe on the 129 background than the C57BL/6 background. Northern blot analysis of skeletal muscle with an exon 6 probe reveals no transcript in the skeletal muscle of homozygous mice. This mutant mouse strain represents a model that may be useful in studies of muscular dystrophy, cardiomyopathy, and smooth muscle dysfunction.

Development
A targeting vector containing a neomycin resistance gene was used to replace exons 3-6 of the gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric animals were backcrossed with C57BL/6 five times by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Sgcb^tm1Kcam allele

006831	129-Sgcbtm1Kcam/J
006833	B6.129-Sgcbtm1Kcam/2J

View Strains carrying   Sgcb^tm1Kcam     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Muscular Dystrophy, Limb-Girdle, Type 2E; LGMD2E - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Sgcb^tm1Kcam/Sgcb^tm1Kcam

        involves: 129S1/Sv * 129X1/SvJ

• muscle phenotype
• abnormal muscle morphology (MGI Ref ID J:60154)
  • homozygotes exhibit loss of the sarcoglycan-sarcospan complex, the dystroglycan complex, and epsilon-sarcoglycan in skeletal, cardiac, and smooth muscles
• abnormal sarcolemma morphology (MGI Ref ID J:60154)
  • at 9 weeks, homozygotes display uptake of Evans blue dye in various skeletal muscles, indicating compromised sarcolemma integrity
• abnormal vascular smooth muscle morphology (MGI Ref ID J:60154)
  • homozygotes display loss of the sarcoglycan-sarcospan complex in vascular smooth muscles leading to vascular perturbation, exaggeration of the muscular dystrophy and initiation of cardiomyopathy
• myocardial necrosis (MGI Ref ID J:60154)
  • as early as 9 weeks, mutant hearts display small necrotic areas
  • at 20 weeks, focal necrotic areas resembling ischemic-like lesions are observed throughout the right and left ventricles; however, active myocardial necrosis is less prominent at 30 weeks
• cardiomyopathy (MGI Ref ID J:60154)
  • homozygotes develop significant cardiomyopathy with extensive regions of necrosis, similar to morphological changes noted in tissue infarcts
• muscle calcification (MGI Ref ID J:60154)
  • as early as 4 weeks, homozygotes exhibit progressive dystrophic calcification in the calf, thigh, and diaphragm muscles
• muscular atrophy (MGI Ref ID J:60154)
• dystrophic muscle (MGI Ref ID J:60154)
  • as early as 4 weeks, homozygotes exhibit progressive dystrophic changes in calf, thigh, and diaphragm muscles including pronounced areas of focal necrosis, dystrophic calcification, endomysial fibrosis, massive fatty infiltration, extensive central nucleation, fiber splitting and hypertrophy
  • consistent with severe muscular dystrophy, 13-16-wk-old homozygotes exhibit increased serum creatine kinase activity
• cardiovascular system phenotype
• abnormal blood vessel morphology (MGI Ref ID J:60154)
  • at 4 weeks, vessels of the mutant heart and diaphragm display a serrated contour, rather than the smoothly tapered vessel walls observed in wild-type mice
• abnormal vascular smooth muscle morphology (MGI Ref ID J:60154)
  • homozygotes display loss of the sarcoglycan-sarcospan complex in vascular smooth muscles leading to vascular perturbation, exaggeration of the muscular dystrophy and initiation of cardiomyopathy
• vascular stenosis (MGI Ref ID J:60154)
  • homozygotes display numerous areas of vascular constrictions often associated with pre- and poststenotic aneurysms in the vasculature of diaphragm, heart, and kidneys
  • vascular constrictions are detected prior to the onset of necrotic changes
• aneurysm (MGI Ref ID J:60154)
  • homozygotes exhibit multiple pre- and poststenotic aneurysms in vessels of the diaphragm, heart, and kidneys
• cardiac fibrosis (MGI Ref ID J:60154)
  • at 30 weeks, mutant hearts exhibit widespread areas of fibrosis
• cardiomyopathy (MGI Ref ID J:60154)
  • homozygotes develop significant cardiomyopathy with extensive regions of necrosis, similar to morphological changes noted in tissue infarcts
• myocardial necrosis (MGI Ref ID J:60154)
  • as early as 9 weeks, mutant hearts display small necrotic areas
  • at 20 weeks, focal necrotic areas resembling ischemic-like lesions are observed throughout the right and left ventricles; however, active myocardial necrosis is less prominent at 30 weeks

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Neuromuscular Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Sgcbtm1Kcam
Allele Name		targeted mutation 1, Kevin P Campbell
Allele Type		Targeted (knock-out)
Mutation Made By		Kevin Campbell,   University of Iowa
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Sgcb, sarcoglycan, beta (dystrophin-associated glycoprotein)
Chromosome		5
Gene Common Name(s)		A3b; AI747103; AI844814; LGMD2E; SGC; beta-SG; expressed sequence AI747103; expressed sequence AI844814;
Molecular Note		A loxP flanked neomycin cassette replaced a genomic fragment that contained exons 3-6. These exons encode part of the transmembrane domain and the extracellular portion of the protein. Northern blot analysis revealed that no transcript was detectable in skeletal muscle of homozygous mice and Western blot and immunohistochemical analysis demonstrated that the protein was absent in the sarcolemma of skeletal muscle derived from homozygous mice. [MGI Ref ID J:60154]

Genotyping

Genotyping Information

Genotyping Protocols

Sgcb^tm1Kcam, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Durbeej M; Cohn RD; Hrstka RF; Moore SA; Allamand V; Davidson BL; Williamson RA; Campbell KP. 2000. Disruption of the beta-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E. Mol Cell 5(1):141-51. [PubMed: 10678176]  [MGI Ref ID J:60154]

Additional References

Sgcb^tm1Kcam related

Cohn RD; Durbeej M; Moore SA; Coral-Vazquez R; Prouty S; Campbell KP. 2001. Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex. J Clin Invest 107(2):R1-7. [PubMed: 11160141]  [MGI Ref ID J:66973]

Crosbie RH; Dovico SA; Flanagan JD; Chamberlain JS; Ownby CL; Campbell KP. 2002. Characterization of aquaporin-4 in muscle and muscular dystrophy. FASEB J 16(9):943-9. [PubMed: 12087055]  [MGI Ref ID J:120469]

Hanft LM; Bogan DJ; Mayer U; Kaufman SJ; Kornegay JN; Ervasti JM. 2007. Cytoplasmic gamma-actin expression in diverse animal models of muscular dystrophy. Neuromuscul Disord 17(7):569-74. [PubMed: 17475492]  [MGI Ref ID J:124551]

Turk R; Sterrenburg E; van der Wees CG; de Meijer EJ; de Menezes RX; Groh S; Campbell KP; Noguchi S; van Ommen GJ; den Dunnen JT; 't Hoen PA. 2006. Common pathological mechanisms in mouse models for muscular dystrophies. FASEB J 20(1):127-9. [PubMed: 16306063]  [MGI Ref ID J:104560]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygotes are intercrossed. Mice with decreased mobility may benefit from ground grain placed in the bottom of the cage.
Mating System	Homozygote x Homozygote         (Female x Male)   14-JUL-09
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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