These NRG-Akita mutant mice are immunodeficient and spontaneously develop hyperglycemia. The strain may be useful as a diabetic host for human islet cells.
Dr. Leonard D. Shultz, The Jackson Laboratory
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Rag1 | recombination activating gene 1 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Ins2 | insulin II |
NRG-Akita mice, which are homozygous for the Rag1tm1Mom and the Il2rgtm1Wjl alleles (males are hemizygous for the X-linked Il2rgtm1Wjl allele) and heterozygous for the Ins2Akita allele, develop spontaneous hyperglycermia. No mature T, B or NK cells are detected in flow cytometric analysis of splenocytes from NRG-Akita mutant mice. Granulocyte and macrophage populations are similar to those seen in NRG mice (Stock No. 7799). NRG-Akita mice develop hyperglycemia between 3 and 5 weeks of age. Histological examination at 3 weeks of age reveals normal pancreas morphology, and routine insulin and glucagon staining. By approximately 32 weeks of age, NRG-Akita mice display disorganized, condensed pancreatic islet architecture, with loss of insulin-positive cells. Euglycemia is restored by subrenal transplantation of mouse or human islets or intrapancreatic transplantation of dissociated mouse islet cells. NRG-Akita mice engrafted with human hematopoietic stem cells (HSC) develop humanized immune systems. Approximately 60% of the human HSC engrafted NRG-Akita mice reject human islet allografts.
To generate this strain NOD.Cg-Rag1tm1Mom Ins2Akita Prf1tm1Sdz/SzJ (Stock No. 008659) mice were crossed with NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (Stock No. 007799) mice. The Prf1tm1Sdz allele was bred out, and the mice were made homozygous for the Rag1tm1Mom and the Il2rgtm1Wjl alleles and heterozygous for the Ins2Akita allele with subsequent crosses.
Allele Name | targeted mutation 1, Peter Mombaerts |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Rag-; Rag1tm1Mom; RAG-1-; Rag1-; RAG1null; Rag-1KO |
Gene Symbol and Name | Rag1, recombination activating gene 1 |
Gene Synonym(s) | |
Site of Expression | expression is seen in bone marrow derived cell lines. |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 2 |
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. |
Mutations Made By | Peter Mombaerts, Max Planck Research Unit for Neurogenetics |
Allele Name | targeted mutation 1, Warren J Leonard |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | [KO]gammac; CD132-; gammac-; gc-; Il2rgtm1Wjll; IL2Rgammanull |
Gene Symbol and Name | Il2rg, interleukin 2 receptor, gamma chain |
Gene Synonym(s) | |
Site of Expression | Primarily lymphoid cells. |
Strain of Origin | 129S4/SvJae |
Chromosome | X |
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. |
Mutations Made By | Dr. Warren Leonard, NHLBI, NIH |
Allele Name | Akita |
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Allele Type | Spontaneous |
Allele Synonym(s) | Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4 |
Gene Symbol and Name | Ins2, insulin II |
Gene Synonym(s) | |
Strain of Origin | C57BL/6NSlc |
Chromosome | 7 |
Molecular Note | In the mutant allele a transition from G-to-A at coding nucleotide 287 disrupts an Fnu4HI site in exon 3. This mutation changed the seventh amino acid in the A chain of mature insulin, Cys96 (TGC), to Tyr (TAC) (p.C96Y). The authors predict that the transition would disrupt a disulfide bond between the A and the B chains and would likely induce a major conformational change in insulin 2 molecules. RT-PCR studies suggest that both normal and mutant Ins2 alleles are transcribed similarly in pancreatic islets of heterozygous mice, although immunofluorescence and immunoblot analyses of heterozygous islets detected reduced levels of insulin and proinsulin. |
The Donating Investigator maintained the strain by crossing female mice that are homozygous for the Rag1tm1Mom and the Il2rgtm1Wjl alleles (not carrying the Ins2Akita allele) with male mice that are homozygous for the Rag1tm1Mom allele, hemizygous for the Il2rgtm1Wjl allele and heterozygous for the Ins2Akita allele.
When using the NRG Akita mouse strain in a publication, please cite the originating article(s) and include JAX stock #014568 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for Rag1<tm1Mom>, Hemizygous or Non carrier for Ins2<Akita>, Homozygous or Hemizygous for Il2rg<tm1Wjl>/SzJ |
Frozen Mouse Embryo | NOD.Cg-Rag1tm1Mom Ins2Akita Il2rgtm1Wjl/SzJ | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Rag1tm1Mom Ins2Akita Il2rgtm1Wjl/SzJ | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Rag1tm1Mom Ins2Akita Il2rgtm1Wjl/SzJ | $3373.50 |
Frozen Mouse Embryo | NOD.Cg-Rag1tm1Mom Ins2Akita Il2rgtm1Wjl/SzJ | $3373.50 |
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