NOD.Cg-Rag1^tm1Mom Dmd^mdx-4Cv Il2rg^tm1Wjl/McalJ

Stock number: 030442
Product name: mdx^4Cv/NRG
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

These mdx^4Cv/NRG mutant mice are an immune-deficient irradiation resistant model of Duchenne muscular dystrophy (DMD) for transplantation experiments with human cells, such as human induced pluripotent stem cells (hiPSC).

Detailed description

These mdx^4Cv/NRG mice are homozygous for the Rag1^null mutation, and homozygous (for females; or hemizygous for males) for the X-linked Dmd^mdx-4Cv and IL2rγ^null mutations. The NRG platform allows transplantation studies related to progressive muscular dystrophy due to defects in the X linked muscular dystrophy 4 gene. No dystrophin protein was detected in gastrocnemius muscle from 6 month old mice by western blot and immunohistochemical analysis. At 6 months of age, mdx^4Cv/NRG mice exhibit impaired mobility, defective membrane integrity in muscle fibers, as assayed by Evans blue dye staining, and increased collagen deposition in gastrocnemius and hamstring muscles, compared to NRG mice. Histological examination of muscle from mutant mice reveals centronucleated fibers, mononuclear cell infiltration and increased variability in fiber size. Females homozygous for all 3 mutations (and males homozygous for Rag1^null ; hemizygous for the X-linked Dmd^mdx-4Cv and IL2rγ^null mutations) are viable and fertile.

Development

B6Ros.Cg-Dmd^mdx-4Cv/J (Stock No. 002378) females were crossed with NOD/ShiLtJ (Stock No. 001976) males. The resulting female progeny were crossed to NOD/ShiLtJ (Stock No. 001976) males for 2 generations. The females generated from this breeding, carrying the Dmd^mdx-4Cv allele were then crossed to NRG, NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ (Stock No. 007799) males for 2 generations. Offspring were intercrossed and bred to be homozygous for the Rag1^null mutation, and homozygous (for females; or hemizygous for males) for the X-linked Dmd^mdx-4Cv and IL2rγ^null mutations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize NRG, NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ, oocytes (Stock No. 007799). Progeny were then intercrossed and bred to be homozygous for the Rag1^null mutation, and homozygous (for females; or hemizygous for males) for the X-linked Dmd^mdx-4Cv and IL2rγ^null mutations.

Allele

Symbol: Rag1^tm1Mom
Name: targeted mutation 1, Peter Mombaerts
MGI accession ID: MGI:1857241
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Rag-; Rag^1tm1Mom; RAG-1-; Rag1^-; RAG1^null; Rag-1KO
Marker symbol: Rag1
Marker name: recombination activating gene 1
Marker synonyms: RAG-1; RNF74
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Site of expression: expression is seen in bone marrow derived cell lines.
Molecular note: A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.

Allele

Symbol: Il2rg^tm1Wjl
Name: targeted mutation 1, Warren J Leonard
MGI accession ID: MGI:1857455
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: [KO]gammac; CD132^-; gammac^-; gc^-; Il2rg^tm1Wjll; IL2Rgamma^null
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
Marker synonyms: [g]c; Ab2-183; Cd132; CIDX; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); gammaC; gc; IL-2RG; IMD4; P64; SCIDX; SCIDX1
Chromosome: X
Strain of origin: 129S4/SvJae
Site of expression: Primarily lymphoid cells.
Molecular note: A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein.

Allele

Symbol: Dmd^mdx-4Cv
Name: X linked muscular dystrophy 4, Verne Chapman
MGI accession ID: MGI:1856331
Generation method: Chemically induced (ENU)
Synonyms: mdx^4cv; mdx^Cv4; mdx4^cv; mdx4cv
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: C3Ha.Cg-Hpr1t^a Pgk1^a
Molecular note: A C to T transition in exon 53 at position 7916 creates a premature stop codon.