Overview

Also Known As:NRG Akita

These NRG-Akita mutant mice are immunodeficient and spontaneously develop hyperglycemia. The strain may be useful as a diabetic host for human islet cells.

Donating Investigator

Dr. Leonard D. Shultz, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Rag1^tm1Mom

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Rag1	recombination activating gene 1

Il2rg^tm1Wjl

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

Research Applications

Hematological Research
Immunology, Inflammation and Autoimmunity Research
Cell Biology Research
Research Tools
Internal/Organ Research
Cancer Research
Endocrine Deficiency Research
Diabetes and Obesity Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

NRG-Akita mice, which are homozygous for the Rag1^tm1Mom and the Il2rg^tm1Wjl alleles (males are hemizygous for the X-linked Il2rg^tm1Wjl allele) and heterozygous for the Ins2^Akita 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.

Development

To generate this strain NOD.Cg-Rag1^tm1Mom Ins2^Akita Prf1^tm1Sdz/SzJ (Stock No. 008659) mice were crossed with NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ (Stock No. 007799) mice. The Prf1^tm1Sdz allele was bred out, and the mice were made homozygous for the Rag1^tm1Mom and the Il2rg^tm1Wjl alleles and heterozygous for the Ins2^Akita allele with subsequent crosses.

Control Suggestions

Depending upon the nature of the experiment, the following may be an appropriate control: wildtype for Ins2^Akita from the colony.

Approximate Controls

001976 NOD/ShiLtJ
003729 NOD.129S7(B6)-Rag1^tm1Mom/J, (NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729) may be an appropriate experimental control strain. )
007799 NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ, (NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ (Stock No. 007799) may be an appropriate experimental control strain.)

Additional Information

Considerations for Choosing Controls

Selected References

Brehm MA; Bortell R; Diiorio P; Leif J; Laning J; Cuthbert A; Yang C; Herlihy M; Burzenski L; Gott B; Foreman O; Powers AC; Greiner DL; Shultz LD. 2010. Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice. Diabetes 59(9):2265-70PubMed: 20570944 MGI: J:167036

View All References

Genetics

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Allele Name	targeted mutation 1, Peter Mombaerts
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Rag-; Rag^1tm1Mom; RAG-1-; Rag1^-; RAG1^null; 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

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Allele Name	targeted mutation 1, Warren J Leonard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	[KO]gammac; CD132^-; gammac^-; gc^-; Il2rg^tm1Wjll; IL2Rgamma^null
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

Ins2^Akita

Allele Symbol: Ins2^Akita

Allele Name	Akita
Allele Type	Spontaneous
Allele Synonym(s)	Akita; Akita^Ins2; Ins2^C96Y; Ins2^Mody; 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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Rag1^tm1Mom related

Hematological Research
- Immunological Defects
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
- Inflammation
  - B and T cell deficiency
Research Tools
- Toxicology Research
  - xenograft/transplant host
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host

Genotype: Ins2^Akita related

Cell Biology Research
- Protein Processing
Endocrine Deficiency Research
- Pancreas Defects
Diabetes and Obesity Research
- Hypoinsulinemia
- Insulin Receptors and Growth Factors
- Type 1 Diabetes (IDDM)
  - MODY, mature onset diabetes of the young
- Impaired Insulin Processing
- Islet Transplantation Studies
- Hyperglycemia

Diabetes and Obesity Research
- Hyperglycemia
- Islet Transplantation Studies
Endocrine Deficiency Research
- Pancreas Defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency

Genotype: Il2rg^tm1Wjl related

Cancer Research
- Growth Factors/Receptors/Cytokines
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines

Mammalian Phenotype Terms by Genotype

References

Brehm MA; Bortell R; Diiorio P; Leif J; Laning J; Cuthbert A; Yang C; Herlihy M; Burzenski L; Gott B; Foreman O; Powers AC; Greiner DL; Shultz LD. 2010. Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice. Diabetes 59(9):2265-70PubMed: 20570944 MGI: J:167036

Additional - Il2rg^tm1Wjl related

Additional - Ins2^Akita related

Additional - Rag1^tm1Mom related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Restriction Enzyme Digest:Ins2
- Pyrosequencing:Ins2
- Standard PCR:Laragen
- End Point Analysis:Ins2
- Probe:Il2rg-PROBE
- Standard PCR:Il2rg
- Standard PCR:Rag1Alternate1
- Probe:Rag1 Probe
- Genotyping resources and troubleshooting
Breeding Considerations

The Donating Investigator maintained the strain by crossing female mice that are homozygous for the Rag1^tm1Mom and the Il2rg^tm1Wjl alleles (not carrying the Ins2^Akita allele) with male mice that are homozygous for the Rag1^tm1Mom allele, hemizygous for the Il2rg^tm1Wjl allele and heterozygous for the Ins2^Akita allele.
- Additional Breeding and Husbandry Support
Mating System
- HOM WILD HOM X HOM HET HEM
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Domestic Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

International Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Homozygous for Rag1<tm1Mom>, Hemizygous or Non carrier for Ins2<Akita>, Homozygous or Hemizygous for Il2rg<tm1Wjl>/SzJ 2 pair minimum

Related Products and Services

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

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Notice regarding distribution of this strain.

Use of MICE by companies or for-profit entities requires a no-fee JAX Leap License prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:NRG Akita

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

Ins2Akita

Allele Symbol: Ins2Akita

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Rag1tm1Mom related

Genotype: Ins2Akita related

Genotype: Il2rgtm1Wjl related

Mammalian Phenotype Terms by Genotype

References

Additional - Il2rgtm1Wjl related

Additional - Ins2Akita related

Additional - Rag1tm1Mom related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Ins2^Akita

Allele Symbol: Ins2^Akita

Genotype: Rag1^tm1Mom related

Genotype: Ins2^Akita related

Genotype: Il2rg^tm1Wjl related

Additional - Il2rg^tm1Wjl related

Additional - Ins2^Akita related

Additional - Rag1^tm1Mom related