NOD.Cg-Rag1^tm1Mom Fanca^em1Dvs Il2rg^tm1Wjl/SzJ

Stock number: 026062
Product name: ARGN
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

ARGN mice lack exon 37 of the Fanconi anemia, complementation group A (Fanca) gene and are maintained on a NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ (Stock No. 007799) background. This strain may have an enhanced ability to be engrafted with human hematopoietic stem cells.

Detailed description

ARGN mice lack exon 37 of the Fanconi anemia, complementation group A (Fanca) gene and are maintained on a NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ (Stock No. 007799) background. FANCA is a member of the Fanconi anemia (FA) complementation group (FANC) which make up a multi-protein nuclear complex involved in cellular responses to DNA damage and germ cell survival. Mutations in this gene are the most common cause of Fanconi anemia, a heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. This strain is an immune deficient model of Fanconi’s Anemia which may be used as recipients for human xenografts, which has been shown to give recipients a profound selective growth advantage.

Of note, female mice homozygous for the Fanca^em1Dvs allele are viable and fertile. Males homozygous for the Fanca^em1Dvs allele are infertile. When maintaining a live colony, HOM HOM HOM females may be bred to HET HOM HOM males, or NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ inbred mice (Stock No. 007799).

Development

The Fanca^em1Dvs allele was created using CRISPR/cas9 endonuclease-mediated genome editing in NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ mouse zygotes (Stock No. 007799).
Specifically, the Fanconi anemia, complementation group A (Fanca) gene on chromosome 8 was targeted with single guide RNAs designed to delete exon 37. The sgRNAs and Cas9 endonuclease were introduced into NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ-derived fertilized eggs by pronuclear injection. Embryos were transferred to pseudopregnant females, and correctly targeted pups (identified by sequencing and PCR) were bred to NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ inbred mice for germline transmission. Resulting ARGN mice from founder 12-1, lacking exon 37, were further bred to NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ inbred mice to develop the colony.

Allele

Symbol: Rag1^tm1Mom
Name: targeted mutation 1, Peter Mombaerts
MGI accession ID: MGI:1857241
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Rag1
Marker name: recombination activating gene 1
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
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
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: Fanca^em1Dvs
Name: endonuclease-mediated mutation 1, David V Serreze
MGI accession ID: MGI:5822992
Generation method: Endonuclease-mediated
Attributes: Hypomorph
Marker symbol: Fanca
Marker name: Fanconi anemia, complementation group A
Chromosome: 8
Strain of origin: NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ
Molecular note: CRISPR/Cas9 technology is used to delete a portion of exon 37.