B10ScSn.Cg-Prkdc^scid Dmd^mdx/J

Stock number: 018018
Product name: MDX/SCID
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools, Sensorineural Research, Virology Research

Description

MDX/SCID mice exhibit necrosis, centrally located nuclei and and the muscle degeneration characteristic of DMD and may be used a dystrophic model for the transplantation of human donor cells to evaluate skeletal muscle regeneration.

Detailed description

The X-linked dystrophin gene (Dmd) is highly expressed in muscle cells and encodes a cytoskeletal protein which localizes to the inner face of the sarcolemma. Dystrophin molecules bind to cytoskeletal F-actin and transmembrane beta-dystroglycan as part of a complex, multimolecular unit that mediates signaling between the intracellular cytoskeleton and the extracellular matrix. The structure and localization also suggest that dystrophin is important for stabilizing the plasma membrane, particularly during contraction. Like human patients who suffer from one of the most common neuromuscular diseases, Duchenne muscular dystrophy (DMD), the Dmd^mdx mutants do not express dystrophin and therefore have been routinely used as an animal model of the disease even though the resultant myopathology is much less severe compared to the human disease course. When combined with the Prkdc^scid allele, there is some amelioration of the mdx phenotype including a reduction in the rate of muscle fibrosis, higher endurance and decreased expression of active TGFB1. However, MDX/SCID mice continue to exhibit necrosis, centrally located nuclei and and the muscle degeneration characteristic of DMD. The MDX/SCID mouse may be used a dystrophic model for the transplantation of human donor cells to evaluate skeletal muscle regeneration.

Development

The spontaneous mutation Dmd^mdx arose just prior to 1977 at the Agricultural Research Council's Poultry Research Centre, U.K., in C57BL/10ScSn mice obtained from M. Festing (MRC Laboratory Animals Centre, Carshalton, Surrey, U.K.). Mice carrying the mdx allele were imported to The Jackson Laboratory in 1984 by Dr. Thomas Roderick, who received them from Dr. Karen Moore (Department of Genetics, University of California, Berkley). In 2000, under the direction of James Cummins at the University of Pittsburgh and Children's Hospital of Pittsburgh, the Prkdc^scid allele from B6.CB17-Prkdc^scid/SzJ was introgressed into C57BL/10ScSn-Dmd^mdx/J for at least 10 generations.

This strain is maintained as homozygous for Prkdc^scid allele and by sibling mating homozygous Dmd^mdx females with hemizygous Dmd^mdx males; mice can breed up to six months of age.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Synonyms: scid
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Marker synonyms: DNAPDcs; DNAPK; DNA-PK; DNAPKc; DNA-PKC; DNA-PKcs; DNPK1; DOXNPH; dxnph; HYRC; HYRC1; IMD26; p350; slip; XRCC7
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
Molecular note: A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*).

Allele

Symbol: Dmd^mdx
Name: X linked muscular dystrophy
MGI accession ID: MGI:1856328
Generation method: Spontaneous
Synonyms: mdx; pke; pyruvate kinase expression
Marker symbol: Dmd
Marker name: dystrophin, muscular dystrophy
Marker synonyms: BMD; CMD3B; DNADMD1; Dp427; Dp71; Duchenne muscular dystrophy; DXS142; DXS164; DXS206; DXS230; DXS239; DXS268; DXS269; DXS270; DXS272; dys; mdx; MRX85; pke; X-linked muscular dystrophy
Chromosome: X
Strain of origin: C57BL/10ScSn
Molecular note: This mutation arose in 1981 in a C57BL/10ScSn colony at University of Leicester. A C-to-T substitution in the CAA codon in exon 23 (ENSMUST00000114000 chrX:g.83803333C>T; c.2983C>T; p.Q995*) results in a termination codon (TAA) in place of a glutamine codon. This allele is predicted to produce a truncated protein.