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; Targeted Mutation; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Kevin Campbell,   University of Iowa

Description
Homozygous alpha-sarcoglycan targeted mutant mice develop a progressive pathology characteristic of limb-girdle muscular dystrophy type 2D starting at one week of age. Necrosis, regeneration, central nucleation, atrophy, hypertrophy, fiber splitting and endomysial fibrosis are observed in their muscle.

When combined with a human epsilon-sarcoglycan transgene driven by a mouse muscle creatine kinase promoter specific to skeletal and heart muscle (as in this compound mutant strain) mice display no overt phenotype with normal behavior and normal muscle force generation. After mild exercise, the compound mutants show an exaggerated fatigue response. Biochemically, the mice show normal levels of nNOS (NOS1) in muscle homogenates, but variable levels in membrane fractions. By immunofluorescence, nNOS (NOS1) is not localized to all muscle membrane fibers.

Development
The Sgca targeted allele was made by replacing exons 2 and 3 of the gene with a neomycin resistance cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. The line was backcrossed five times to C57BL/6 by the donating laboratory.

The mouse muscle creatine kinase promoter specific for skeletal and cardiac muscle drives expression of the full-length human epsilon-sarcoglycan cDNA in the transgenic portion of this strain. This is Line 1 of the transgenic line. The transgenic vector was introduced to B6SJLF1 embryos. The mutation was backcrossed twice to C57BL/6 then crossed to the Sgca line mentioned above for 13 generations by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ckm

014146	B6.Cg-Tg(Ckm-DYSF)3Kcam/J
012379	B6.Cg-Tg(Ckm-Ppara)HEDpk/J
006475	B6.FVB(129S4)-Tg(Ckmm-cre)5Khn/J
006781	C57BL/6-Tg(Ckm-DGAT2)10Far/J
008231	C57BL/6-Tg(Ckm-Ppargc1a)31Brsp/J
021199	FVB-Tg(Ckm-Chrnd*S268F)1Cgz/J
019931	FVB-Tg(Ckm-Chrne*L269F)5Cgz/J
016618	FVB-Tg(Ckm-IGF1R*K1003R)1Dlr/J
008737	FVB-Tg(Ckm-Ppargc1b)T37Brsp/J
006405	FVB-Tg(Ckmm-cre)5Khn/J

View Strains carrying other alleles of Ckm     (10 strains)

Strains carrying other alleles of Sgca

008275

B6.129S6-Sgcatm2Kcam/J

View Strains carrying other alleles of Sgca     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Muscular Dystrophy, Limb-Girdle, Type 2D; LGMD2D   (SGCA) - Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Myoclonic Dystonia   (SGCE)

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.

Sgca^tm1Kcam/Sgca^tm1Kcam Tg(Ckm-SGCE)1Kcam/0

        involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * SJL

• cardiovascular system phenotype
• cardiomyopathy   (MGI Ref ID J:177563)
• muscle phenotype
• cardiomyopathy   (MGI Ref ID J:177563)

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
      type 2B

Neurobiology Research
Muscular Dystrophy
      Limb-Girdle type

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Sgcatm1Kcam
Allele Name		targeted mutation 1, Kevin P Campbell
Allele Type		Targeted (knock-out)
Common Name(s)		KO/KO; Sgcanull; Sgcatm594Kcam; alphaSG-;
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		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		Replacement of 902 bp including exons 2 and 3 with a neomycin cassette. No mRNA was detectable in Northern blots of total RNA derived from skeletal muscle tissue of homozygous mutants, and no protein was detected in Western blots in membrane enriched preparations of skeletal muscle. [MGI Ref ID J:49992]
Allele Symbol		Tg(Ckm-SGCE)1Kcam
Allele Name		transgene insertion 1, Kevin Campbell
Allele Type		Transgenic (random, expressed)
Common Name(s)		MCKeSG;
Strain of Origin		(C57BL/6 x SJL)F1
Expressed Gene		SGCE, sarcoglycan, epsilon, human
Promoter		Ckm, creatine kinase, muscle, mouse, laboratory
Molecular Note		The mouse muscle creatine kinase promoter specific for skeletal and cardiac muscle drives expression of the full-length human epsilon sarcoglycan in this transgene construct. [MGI Ref ID J:144084]

Genotyping

Genotyping Information

Genotyping Protocols

Sgca^tm1Kcam, Standard PCR
Tg(Ckm-SGCE)1Kcam, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kobayashi YM; Rader EP; Crawford RW; Iyengar NK; Thedens DR; Faulkner JA; Parikh SV; Weiss RM; Chamberlain JS; Moore SA; Campbell KP. 2008. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature 456(7221):511-5. [PubMed: 18953332]  [MGI Ref ID J:144084]

Additional References

Sgca^tm1Kcam related

Bartoli M; Bourg N; Stockholm D; Raynaud F; Delevacque A; Han Y; Borel P; Seddik K; Armande N; Richard I. 2006. A mouse model for monitoring calpain activity under physiological and pathological conditions. J Biol Chem 281(51):39672-80. [PubMed: 17056592]  [MGI Ref ID J:117658]

Bartoli M; Gicquel E; Barrault L; Soheili T; Malissen M; Malissen B; Vincent-Lacaze N; Perez N; Udd B; Danos O; Richard I. 2008. Mannosidase I inhibition rescues the human alpha-sarcoglycan R77C recurrent mutation. Hum Mol Genet 17(9):1214-21. [PubMed: 18252745]  [MGI Ref ID J:133929]

Beedle AM; Nienaber PM; Campbell KP. 2007. Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein complex. J Biol Chem 282(23):16713-7. [PubMed: 17452335]  [MGI Ref ID J:122734]

Cassano M; Biressi S; Finan A; Benedetti L; Omes C; Boratto R; Martin F; Allegretti M; Broccoli V; Cusella De Angelis G; Comoglio PM; Basilico C; Torrente Y; Michieli P; Cossu G; Sampaolesi M. 2008. Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis. PLoS ONE 3(9):e3223. [PubMed: 18795097]  [MGI Ref ID J:144095]

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]

Crosbie RH; Lebakken CS; Holt KH; Venzke DP; Straub V; Lee JC; Grady RM; Chamberlain JS; Sanes JR; Campbell KP. 1999. Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex. J Cell Biol 145(1):153-65. [PubMed: 10189375]  [MGI Ref ID J:77615]

Dellavalle A; Maroli G; Covarello D; Azzoni E; Innocenzi A; Perani L; Antonini S; Sambasivan R; Brunelli S; Tajbakhsh S; Cossu G. 2011. Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nat Commun 2:499. [PubMed: 21988915]  [MGI Ref ID J:188175]

Duclos F; Straub V; Moore SA; Venzke DP; Hrstka RF; Crosbie RH; Durbeej M; Lebakken CS; Ettinger AJ; van der Meulen J; Holt KH; Lim LE; Sanes JR; Davidson BL; Faulkner JA; Williamson R; Campbell KP. 1998. Progressive muscular dystrophy in alpha-sarcoglycan-deficient mice. J Cell Biol 142(6):1461-71. [PubMed: 9744877]  [MGI Ref ID J:49992]

Fernandez K; Serinagaoglu Y; Hammond S; Martin LT; Martin PT. 2010. Mice lacking dystrophin or alpha sarcoglycan spontaneously develop embryonal rhabdomyosarcoma with cancer-associated p53 mutations and alternatively spliced or mutant Mdm2 transcripts. Am J Pathol 176(1):416-34. [PubMed: 20019182]  [MGI Ref ID J:156447]

Fiaschi T; Tedesco FS; Giannoni E; Diaz-Manera J; Parri M; Cossu G; Chiarugi P. 2010. Globular adiponectin as a complete mesoangioblast regulator: role in proliferation, survival, motility, and skeletal muscle differentiation. Mol Biol Cell 21(6):848-59. [PubMed: 20089845]  [MGI Ref ID J:165080]

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]

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]

Lancioni A; Luisa Rotundo I; Monique Kobayashi Y; D'Orsi L; Aurino S; Nigro G; Piluso G; Acampora D; Cacciottolo M; Campbell KP; Nigro V. 2011. Combined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac dystrophin complex. Hum Mol Genet 20(23):4644-54. [PubMed: 21890494]  [MGI Ref ID J:177563]

Laure L; Suel L; Roudaut C; Bourg N; Ouali A; Bartoli M; Richard I; Daniele N. 2009. Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling. FEBS J 276(3):669-84. [PubMed: 19143834]  [MGI Ref ID J:147891]

Quattrocelli M; Palazzolo G; Floris G; Schoffski P; Anastasia L; Orlacchio A; Vandendriessche T; Chuah MK; Cossu G; Verfaillie C; Sampaolesi M. 2011. Intrinsic cell memory reinforces myogenic commitment of pericyte-derived iPSCs. J Pathol 223(5):593-603. [PubMed: 21341275]  [MGI Ref ID J:170841]

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]

Xu R; DeVries S; Camboni M; Martin PT. 2009. Overexpression of Galgt2 reduces dystrophic pathology in the skeletal muscles of alpha sarcoglycan-deficient mice. Am J Pathol 175(1):235-47. [PubMed: 19498002]  [MGI Ref ID J:150058]

Tg(Ckm-SGCE)1Kcam related

Lancioni A; Luisa Rotundo I; Monique Kobayashi Y; D'Orsi L; Aurino S; Nigro G; Piluso G; Acampora D; Cacciottolo M; Campbell KP; Nigro V. 2011. Combined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac dystrophin complex. Hum Mol Genet 20(23):4644-54. [PubMed: 21890494]  [MGI Ref ID J:177563]

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 donating investigator crosses homozygous Sgca targeted mutant/hemizygous SGCE transgenic males with homozygous Sgca targeted mutant females to maintain a colony.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
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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