B10.Cg-Dmd^mdx Tg(Myh6-DMD*)#Dua/Mmjax

Stock number: 027820
Research areas: Cell Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

Mice homozygous/hemizygous for the spontaneous Dmd^mdx allele and homozygous for the human micro-dystrophin transgene exhibit partially improved cardiac muscle function and muscle histopathology as compared to mdx mice and may be useful for studying Duchenne muscular dystrophy.

Detailed description

Duchenne muscular dystrophy (DMD) is a progressive muscular disorder caused by an imbalance between muscle degeneration and regeneration resulting in muscle degeneration, necrosis, accumulation of fat and fibrosis, and insufficient regeneration/loss of myofibers. The genetic cause of DMD are mutations of the dystrophin muscular dystrophy gene (DMD) on the X chromosome. The Dmd^mdx mutation in mice has a termination codon in exon 23 that is predicted to result in a truncated protein. Homozygous females and hemizygous males develop the myopathic features of DMD; although the myopathology is both less severe than the human disease course.

The Tg(Myh6-DMD*)#Dua transgene carries a deletion of repeat 4 through repeat 19 and the C-terminus under the control of the rat cardiac muscle specific alpha myosin (Myh6 or α-MHC) promoter. When the transgene is combined with the mdx allele, the donating investigator reports that homozygous mice exhibit partially improved cardiac muscle function and histopathology as compared to mdx mice.

Development

The spontaneous mutation "X chromosome-linked muscular dystrophy" (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.). The mdx mutation was identified as a C-to-T transition resulting in a termination codon at position 2983 (ENSMUST00000114000 chrX:g.83803333 C>T; p.Q995*) within exon 23 of the dystrophin muscular dystrophy gene (Dmd) on the X chromosome [note that Sicinski et al., 1989 originally reported termination codon at position 3185].

The transgenic construct contains a full length human dystrophin gene modified by the deletion of repeat 4 through repeat 19 and the C-terminus to generate a micro-dystrophin cDNA under the control of the rat cardiac muscle specific alpha myosin (Myh6 or α-MHC) promoter. The transgene was microinjected into the pronucleus of fertilized FVB/N mouse eggs. Founder lines 24 and 25 were combined and crossed to C57BL/10ScSn-Dmd^mdx/J mice for more than 9 generations.

Allele

Symbol: Dmd^mdx
Name: X linked muscular dystrophy
MGI accession ID: MGI:1856328
Generation method: Spontaneous
Synonyms: pke; mdx; pyruvate kinase expression
Marker symbol: Dmd
Marker name: dystrophin, 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.

Allele

Symbol: Tg(Myh6-DMD*)#Dua
Name: transgene insertion, Dongsheng Duan
MGI accession ID: MGI:5641674
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Myh6-DMD*)#Dua
Marker name: transgene insertion, Dongsheng Duan
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: DMD,dystrophin,human
Molecular note: The transgenic construct contains a full length human dystrophin gene modified by the deletion of repeat 4 through repeat 19 and the C-terminus to generate a micro-dystrophin cDNA under the control of the rat cardiac muscle specific alpha myosin (Myh6 or alpha-MHC) promoter. Founder lines 24 and 25 were combined.