NOD.Cg-Rag1^tm1Mom Dysf^prmd Il2rg^tm1Wjl/McalJ

Stock number: 029663
Product name: BlAJ/NRG
Strain synonyms: BlAJ/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 BlAJ/NRG mutant mice are an immune-deficient model of limb-girdle muscular dystrophy type 2B (LGMD2B) for transplantation experiments with human cells, such as human induced pluripotent stem cells (hiPSC).

Detailed description

These BlAJ/NRG mice are homozygous for the Rag1^null and Dysf^prmd mutations, and homozygous (for females; or hemizygous for males) for the X-linked IL2rγ^null mutation. The NRG platform allows transplantation studies related to progressive muscular dystrophy due to defects in the dysferlin gene. No dysferlin protein was detected in gastrocnemius muscle from 6 month old mice by immunohistochemical analysis. BlAJ/NRG mice exhibit progressive muscular dystrophy phenotype similar to the phenotype observed in B6.A-Dysf^prmd/GeneJ (Bl/AJ) (Stock No. 012767) mice. In gene therapy experiments, a luciferase transgene, which is rejected in immune-competent mice, was retained by the BlAJ/NRG mice for more than 6 months. Females homozygous for all 3 mutations (and males homozygous for Rag1^null and Dysf^prmd; hemizygous for the X-linked IL2rγ^null mutation) are viable and fertile.

Development

B6.A-Dysf^prmd/GeneJ (Bl/AJ) 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 Dysf^prmd 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 and Dysf^prmd mutations, and homozygous (for females; or hemizygous for males) for the X-linked IL2rγ^null mutation. 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 and Dysf^prmd mutations, and homozygous (for females; or hemizygous for males) for the X-linked IL2rγ^null mutation.

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: Dysf^prmd
Name: progressive muscular dystrophy
MGI accession ID: MGI:3055150
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Dysf
Marker name: dysferlin
Marker synonyms: 2310004N10Rik; FER1L1; LGMD2B; LGMDR2; MMD1
Chromosome: 6
Strain of origin: A/J
Molecular note: A retrotransposon insertion occurred within intron 4, causing aberrant splicing of the gene. Protein was abolished as shown by Northern blot and immunoblot analysis. The insertion was 6000bp in size. This allele was found only in A/J mice, not in A/WySnJ, A/HeJ, C57BL/6J, SJL/J, SWR/J or 129/SvJ mice.