Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N6+ (23-JUL-08)   Donating Investigator Kevin Campbell,   University of Iowa

Description
Mice homozygous for this targeted mutation are viable and fertile. A loxP-flanked neomycin resistance cassette blocks expression of a His77Cys (H77C) missense mutation introduced into exon 3 of the gene. Alpha-sarcoglycan mRNA is not detected by RT-PCR, and protein is not detected by Western blot or immunofluorescence staining of skeletal muscle. The mice develop progressive muscular dystrophy as early as six weeks of age with typical pathological changes in skeletal muscle and an elevation of serum creatine kinase activity.

After germline- or striated muscle-specific Cre-mediated excision of the floxed neomycin cassette, the H77C missense mutation is expressed in the sarcolemma of striated muscles, and homozygotes do not show any sign of muscular dystrophy as late as 88 weeks of age.

For example, when crossed to a strain expressing Cre recombinase in skeletal and cardiac muscle (see Stock No. 006475), this mutant mouse strain may be useful in muscular dystrophy research.

Development
A targeting vector was designed to introduce an H77C (TGC->CAC) missense substitution in exon 3, and place a loxP-flanked pgk-neomycin resistance cassette (in opposite transcriptional orientation) into intron 3 of the gene. The targeting vector was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric mice were obtained. The line was backcrossed to C57BL/6 for five generations by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

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.

Sgca^tm2Kcam/Sgca^tm2Kcam

        either: (129S6/SvEvTac-Sgca^tm2Kcam) or (involves: 129S6/SvEvTac * C57BL/6J)

• muscle phenotype
• abnormal muscle contractility (MGI Ref ID J:130252)
• abnormal muscle fiber morphology (MGI Ref ID 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 (MGI Ref ID J:130252)
  • membrane damage is exhibited in quadriceps muscles as shown by uptake of Evans blue dye into fibers between 3 and 12 months
• dystrophic muscle (MGI Ref ID J:130252)
  • mice develop muscular dystrophy essentially identical to that show by Sgca^tm1Kcam homozygotes
• increased muscle weight (MGI Ref ID J:130252)
• muscle calcification (MGI Ref ID J:130252)
• homeostasis/metabolism phenotype
• abnormal protein level (MGI Ref ID 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

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Sgca^tm2Kcam/Sgca^tm2Kcam Tg(Ckmm-cre)5Khn/0

        either: (involves: 129S4/SvJae * 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6J * FVB)   (conditional)

• muscle phenotype
• *normal* muscle phenotype (MGI Ref ID J:130252)
  • conditional mutants fail to develop muscular dystrophy pathology; striated and cardiac muscle show expression of mutant alpha-sarcoglycan, as well as sarcospan
  • percentage of fibers with centrally located nuclei are normalized to levels of heterozygous non-transgenic controls
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:130252)
  • serum creatine kinase levels are normalized

View Research Applications

Research Applications

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

Mouse/Human Gene Homologs
muscular dystrophy, limb-girdle

Neurobiology Research
Neuromuscular Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Sgcatm2Kcam
Allele Name		targeted mutation 2, Kevin Campbell
Allele Type		Targeted (Floxed/Frt)
Mutation Made By		Kevin Campbell,   University of Iowa
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		W4
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Sgca, sarcoglycan, alpha (dystrophin-associated glycoprotein)
Chromosome		11
Gene Common Name(s)		50-DAG; 50DAG; A2; ADL; Asg; DAG2; DMDA2; LGMD2D; SCARMD1; adhalin;
Molecular Note		A targeting vector was designed to introduce an H77C (TGC->CAC) missense substitution in exon 3, and place a loxP-flanked pgk-neomycin resistance cassette (in opposite transcriptional orientation) into intron 3 of the gene. Alpha-sarcoglycan mRNA is not detected by RT-PCR, and protein is not detected by Western blot or immunofluorescence staining of skeletal muscle. [MGI Ref ID J:130252]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), STD PCR, vers. 1
Sgca^tm2Kcam, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Kobuke K; Piccolo F; Garringer KW; Moore SA; Sweezer E; Yang B; Campbell KP. 2008. A Common Disease-Associated Missense Mutation in Alpha-Sarcoglycan Fails to Cause Muscular Dystrophy in Mice. Hum Mol Genet :. [PubMed: 18252746]  [MGI Ref ID J:130252]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, homozygotes may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)
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 ~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 48 hours of 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.

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

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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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In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

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.