Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

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. Species laboratory mouse Generation N10+F2+N1p (16-MAY-04) Generation Definitions   Donating Investigator Elizabeth McNally,   University of Chicago

Description
Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. No gene product (protein) is immunodetected in skeletal muscle microsomal preparations. At 8 weeks of age there is an onset of sudden mortality, with a 50% survival rate at 28 weeks. Elevated creatine kinase serum levels are indicative of striated muscle degeneration. Histopathology of skeletal muscle tissue reveals degeneration and regeneration of muscle fibers, inflammatory infiltrate, perivascular fibrosis and calcification. At 12 weeks of age, cardiac muscle tissue also begins to show degeneration, inflammatory infiltration and perivascular fibrosis. Myofiber membranes have permeability defects as assessed by Evans blue dye uptake into myofiber cytoplasm. Skeletal muscle of mutant mice have an enhanced sensitivity to mechanically induced sarcolemmal damage. This mutant mouse strain may be useful in studies of limb girdle muscular dystrophy and cardiomyopathy.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2, which encodes the initiation site, cytoplasmic domain and transmembrane domain. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Cardiomyopathy, Dilated, 1L; CMD1L
Muscular Dystrophy, Limb-Girdle, Type 2F; LGMD2F

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Sgcd^tm1Mcn/Sgcd^tm1Mcn

        involves: 129S1/Sv * 129T2/SvEmsJ * 129X1/SvJ

• mortality/aging
• premature death
  • beginning at 8 weeks of age, begin to die suddenly   (MGI Ref ID J:76730)
  • premature mortality is also noted at 12, 16, and 28 weeks of age, with a 50% survival rate at 28 weeks of age   (MGI Ref ID J:76730)
• muscle phenotype
• abnormal muscle physiology
  • muscles exhibit pronounced Evans blue dye uptake, indicating alterations in membrane permeability of muscles   (MGI Ref ID J:76730)
• • abnormal muscle contractility
    • show a 42% drop in force generation over a five eccentric contraction protocol, however twich and tetanic force generation is normal   (MGI Ref ID J:76730)
  • cardiomyopathy
    • beginning at 12 weeks of age, observe signs of cardiac muscle degeneration as indicated by areas of cell death and inflammatory infiltrate   (MGI Ref ID J:76730)
• dystrophic muscle
  • all skeletal muscles show dystrophic changes   (MGI Ref ID J:76730)
  • regional degeneration and regeneration of muscle fibers is common and accompanied by an inflammatory infiltrate   (MGI Ref ID J:76730)
• muscle degeneration
  • skeletal and cardiac muscle degeneration   (MGI Ref ID J:76730)
• cardiovascular system phenotype
• cardiomyopathy
  • beginning at 12 weeks of age, observe signs of cardiac muscle degeneration as indicated by areas of cell death and inflammatory infiltrate   (MGI Ref ID J:76730)
• perivascular fibrosis
  • frequent occurrence of perivascular fibrosis   (MGI Ref ID J:76730)
• homeostasis/metabolism phenotype
• increased circulating creatine kinase level
  • elevation in serum creatine kinase levels   (MGI Ref ID J:76730)

View Research Applications

Research Applications

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

Neurobiology Research
Muscular Dystrophy
      Limb-Girdle type

Sgcd^tm1Mcn related

Cardiovascular Research
Heart Abnormalities
      cardiomyopathy

Mouse/Human Gene Homologs
muscular dystrophy, limb-girdle
      type 2F

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Sgcdtm1Mcn
Allele Name		targeted mutation 1, Elizabeth M McNally
Allele Type		Targeted (knock-out)
Common Name(s)		Scgd-; dsg-;
Mutation Made By		Elizabeth McNally,   University of Chicago
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		Sgcd, sarcoglycan, delta (dystrophin-associated glycoprotein)
Chromosome		11
Gene Common Name(s)		35DAG; CMD1L; DAGD; SG-delta; SGCDP; SGD; delta-SG;
Molecular Note		A neomycin selection cassette was used to replace exon 2, which encodes the translation initiation codon and the cytoplasmic and transmembrane domains. Northern analysis showed that message was not transcribed in skeletal muscle of homozygous mutant mice. The lack of protein in immunoblots further confirmed complete inactivation. [MGI Ref ID J:76730]

Genotyping

Genotyping Information

Genotyping Protocols

Sgcd^tm1Mcn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hack AA; Lam MY; Cordier L; Shoturma DI; Ly CT; Hadhazy MA; Hadhazy MR; Sweeney HL; McNally EM. 2000. Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin-glycoprotein complex. J Cell Sci 113(Pt 14):2535-44. [PubMed: 10862711]  [MGI Ref ID J:76730]

Additional References

Sgcd^tm1Mcn related

Goldstein JA; Kelly SM; Lopresti PP; Heydemann A; Earley JU; Ferguson EL; Wolf MJ; McNally EM. 2011. SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy. Hum Mol Genet 20(5):894-904. [PubMed: 21138941]  [MGI Ref ID J:169051]

Goonasekera SA; Lam CK; Millay DP; Sargent MA; Hajjar RJ; Kranias EG; Molkentin JD. 2011. Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle. J Clin Invest 121(3):1044-52. [PubMed: 21285509]  [MGI Ref ID J:171822]

Heydemann A; Huber JM; Kakkar R; Wheeler MT; McNally EM. 2004. Functional nitric oxide synthase mislocalization in cardiomyopathy. J Mol Cell Cardiol 36(2):213-23. [PubMed: 14871549]  [MGI Ref ID J:101900]

Li D; Long C; Yue Y; Duan D. 2009. Sub-physiological sarcoglycan expression contributes to compensatory muscle protection in mdx mice. Hum Mol Genet 18(7):1209-20. [PubMed: 19131360]  [MGI Ref ID J:146188]

Li D; Yue Y; Lai Y; Hakim CH; Duan D. 2011. Nitrosative stress elicited by nNOSmicro delocalization inhibits muscle force in dystrophin-null mice. J Pathol 223(1):88-98. [PubMed: 21125668]  [MGI Ref ID J:167308]

Lorts A; Schwanekamp JA; Baudino TA; McNally EM; Molkentin JD. 2012. Deletion of periostin reduces muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-beta pathway. Proc Natl Acad Sci U S A 109(27):10978-83. [PubMed: 22711826]  [MGI Ref ID J:186422]

Millay DP; Goonasekera SA; Sargent MA; Maillet M; Aronow BJ; Molkentin JD. 2009. Calcium influx is sufficient to induce muscular dystrophy through a TRPC-dependent mechanism. Proc Natl Acad Sci U S A 106(45):19023-8. [PubMed: 19864620]  [MGI Ref ID J:154908]

Millay DP; Maillet M; Roche JA; Sargent MA; McNally EM; Bloch RJ; Molkentin JD. 2009. Genetic manipulation of dysferlin expression in skeletal muscle: novel insights into muscular dystrophy. Am J Pathol 175(5):1817-23. [PubMed: 19834057]  [MGI Ref ID J:154690]

Millay DP; Sargent MA; Osinska H; Baines CP; Barton ER; Vuagniaux G; Sweeney HL; Robbins J; Molkentin JD. 2008. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat Med 14(4):442-7. [PubMed: 18345011]  [MGI Ref ID J:133679]

Parsons SA; Millay DP; Sargent MA; McNally EM; Molkentin JD. 2006. Age-dependent effect of myostatin blockade on disease severity in a murine model of limb-girdle muscular dystrophy. Am J Pathol 168(6):1975-85. [PubMed: 16723712]  [MGI Ref ID J:110118]

Parsons SA; Millay DP; Sargent MA; Naya FJ; McNally EM; Sweeney HL; Molkentin JD. 2007. Genetic disruption of calcineurin improves skeletal muscle pathology and cardiac disease in a mouse model of limb-girdle muscular dystrophy. J Biol Chem 282(13):10068-78. [PubMed: 17289669]  [MGI Ref ID J:121162]

Porter JD; Merriam AP; Hack AA; Andrade FH; McNally EM. 2001. Extraocular muscle is spared despite the absence of an intact sarcoglycan complex in gamma- or delta-sarcoglycan-deficient mice. Neuromuscul Disord 11(2):197-207. [PubMed: 11257478]  [MGI Ref ID J:103119]

Schoensiegel F; Bekeredjian R; Schrewe A; Weichenhan D; Frey N; Katus HA; Ivandic BT. 2007. Atrial natriuretic peptide and osteopontin are useful markers of cardiac disorders in mice. Comp Med 57(6):546-53. [PubMed: 18246866]  [MGI Ref ID J:141626]

Solares-Perez A; Sanchez JA; Zentella-Dehesa A; Garcia MC; Coral-Vazquez RM. 2010. Intracellular Ca2+ transients in delta-sarcoglycan knockout mouse skeletal muscle. Biochim Biophys Acta 1800(3):373-9. [PubMed: 19931597]  [MGI Ref ID J:164821]

Townsend D; Yasuda S; McNally E; Metzger JM. 2011. Distinct pathophysiological mechanisms of cardiomyopathy in hearts lacking dystrophin or the sarcoglycan complex. FASEB J 25(9):3106-14. [PubMed: 21665956]  [MGI Ref ID J:175721]

Wheeler MT; Korcarz CE; Collins KA; Lapidos KA; Hack AA; Lyons MR; Zarnegar S; Earley JU; Lang RM; McNally EM. 2004. Secondary coronary artery vasospasm promotes cardiomyopathy progression. Am J Pathol 164(3):1063-71. [PubMed: 14982859]  [MGI Ref ID J:88456]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	The resulting chimeric male animals were crossed to 129T2/SvEmsJ (Stock No. 002065) mice and then backcrossed to C57BL/6 for more than 10 generations.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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