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Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N10+F2+N1p (16-MAY-04) 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 | ||
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| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Congenic Nomenclature
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms
Cardiomyopathy, Dilated, 1L; CMD1L - Models with phenotypic similarity to human disease where etiologies involve orthologs.1 Muscular Dystrophy, Limb-Girdle, Type 2F; LGMD2F - 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.
Sgcdtm1Mcn/Sgcdtm1Mcn
involves: 129S1/Sv * 129T2/SvEmsJ * 129X1/SvJ
- life span-post-weaning/aging
- premature death (MGI Ref ID 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 phenotype
- abnormal muscle physiology (MGI Ref ID J:76730)
- muscles exhibit pronounced Evans blue dye uptake, indicating alterations in membrane permeability of muscles
- abnormal muscle contractility (MGI Ref ID J:76730)
- show a 42% drop in force generation over a five eccentric contraction protocol, however twich and tetanic force generation is normal
- cardiomyopathy (MGI Ref ID J:76730)
- beginning at 12 weeks of age, observe signs of cardiac muscle degeneration as indicated by areas of cell death and inflammatory infiltrate
- dystrophic muscle (MGI Ref ID 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 (MGI Ref ID J:76730)
- skeletal and cardiac muscle degeneration
- cardiovascular system phenotype
- cardiomyopathy (MGI Ref ID 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 phenotype
- abnormal circulating enzyme level (MGI Ref ID J:76730)
- elevation in serum creatine kinase levels
- other phenotype
- fibrosis (MGI Ref ID J:76730)
- frequent occurrence of perivascular fibrosis
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Sgcdtm1Mcn related
Cardiovascular Research
Heart Abnormalities (cardiomyopathy)
Mouse/Human Gene Homologs
muscular dystrophy, limb-girdle (type 2F)
| 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; MGC22567; 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 Protocols
Sgcdtm1Mcn, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
Sgcdtm1Mcn relatedHeydemann 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]
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]
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]
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 for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 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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