Description

Strain Information

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 Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

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.

Sgcd^tm1Mcn/Sgcd^tm1Mcn

        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:

Sgcd^tm1Mcn related

Cardiovascular Research
Heart Abnormalities (cardiomyopathy)

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

Genes & Alleles

Gene & Allele Information

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

Genotyping Information

Genotyping Protocols

Sgcd^tm1Mcn, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

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]

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]

Health & husbandry

Health & Colony Maintenance Information

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.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	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.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.