Strain Name:

NOD.Cg-Rag1tm1Mom Ins2Akita Il2rgtm1Wjl/SzJ

Stock Number:

014568

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Availability:

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Use Restrictions Apply, see Terms of Use
These NRG-Akita mutant mice are immunodeficient and spontaneously develop hyperglycemia. The strain may be useful as a diabetic host for human islet cells.

Description

Strain Information

Type Congenic; Mutant Strain; Spontaneous Mutation; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHOM WILD HOM X HOM HET HEMI
Specieslaboratory mouse
Generation?+F6pN1F2 (08-JUL-14)
Generation Definitions
 
Donating InvestigatorDr. Leonard D. Shultz,   The Jackson Laboratory

Description
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.

Development
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.

Control Information

  Control
   003729 NOD.129S7(B6)-Rag1tm1Mom/J (approximate) NOD.129S7(B6)-Rag1tm1Mom/J (Stock No. 003729) may be an appropriate experimental control strain.
   007799 NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (approximate) NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (Stock No. 007799) may be an appropriate experimental control strain.
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Il2rgtm1Wjl     (19 strains)

View Strains carrying   Ins2Akita     (11 strains)

View Strains carrying   Rag1tm1Mom     (24 strains)

View Strains carrying other alleles of Il2rg     (9 strains)

View Strains carrying other alleles of Ins2     (7 strains)

Strains carrying other alleles of Rag1
007790   B6;129P2-Rag1/Rag2tm1Mnz/J
View Strains carrying other alleles of Rag1     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

View Research Applications

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

Diabetes and Obesity Research
Hyperglycemia
Islet Transplantation Studies

Endocrine Deficiency Research
Pancreas Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      B and T cell deficiency

Il2rgtm1Wjl related

Cancer Research
Growth Factors/Receptors/Cytokines

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

Ins2Akita related

Cell Biology Research
Protein Processing

Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Islet Transplantation Studies
Type 1 Diabetes (IDDM)
      MODY, mature onset diabetes of the young

Endocrine Deficiency Research
Pancreas Defects

Rag1tm1Mom related

Cancer Research
Toxicology
      B and T cell deficiency, xenograft/transplant host

Hematological Research
Immunological Defects
      B and T cell deficiency

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      B and T cell deficiency
Inflammation
      B and T cell deficiency
T Cell Receptor Signaling Defects
      B and T cell deficiency

Internal/Organ Research
Lymphoid Tissue Defects
      B and T cell deficiency

Research Tools
Cancer Research
      B and T cell deficiency, xenograft/transplant host
Toxicology Research
      xenograft/transplant host

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Il2rgtm1Wjl
Allele Name targeted mutation 1, Warren J Leonard
Allele Type Targeted (Null/Knockout)
Common Name(s) CD132-; IL2Rgammanull; Il2rgtm1Wjll; [KO]gammac; gammac-; gc-;
Mutation Made ByDr. Warren Leonard,   NHLBI, NIH
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Il2rg, interleukin 2 receptor, gamma chain
Chromosome X
Gene Common Name(s) Ab2-183; CD132; CIDX; IL-2RG; IMD4; P64; SCIDX; SCIDX1; [g]c; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); gc;
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. [MGI Ref ID J:24117]
 
Allele Symbol Ins2Akita
Allele Name Akita
Allele Type Spontaneous
Common Name(s) Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4;
Strain of OriginC57BL/6NSlc
Gene Symbol and Name Ins2, insulin II
Chromosome 7
Gene Common Name(s) AA986540; IDDM1; IDDM2; ILPR; IRDN; Ins-2; InsII; MODY10; Mody; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4;
General Note Phenotypic Similarity to Human Syndrome: Type 1 Diabetic Macrovascular Disease (J:174983)
Molecular Note In the mutant allele a transition from G to A at nucleotide 1907 disrupted 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). 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. [MGI Ref ID J:51935]
 
Allele Symbol Rag1tm1Mom
Allele Name targeted mutation 1, Peter Mombaerts
Allele Type Targeted (Null/Knockout)
Common Name(s) RAG-1-; RAG1null; Rag-; Rag-1KO; Rag1-; Rag1tm1Mom;
Mutation Made By Peter Mombaerts,   Max Planck Research Unit for Neurogenetics
Strain of Origin129S7/SvEvBrd-Hprt<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt<+>
Site of Expressionexpression is seen in bone marrow derived cell lines.
Gene Symbol and Name Rag1, recombination activating gene 1
Chromosome 2
Gene Common Name(s) RAG-1; RNF74; Rag-1;
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. [MGI Ref ID J:1934] [MGI Ref ID J:96036]

Genotyping

Genotyping Information

Genotyping Protocols

Il2rgtm1Wjl-PROBE,

Probe


Ins2Akita, End Point Analysis
Ins2Akita, Pyrosequencing
Ins2Akita, Restriction Enzyme Digest
Prf1tm1Sdz, Melt Curve Analysis
Prf1tm1Sdz, Standard PCR
Rag1tm1Mom, High Resolution Melting


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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):2265-70. [PubMed: 20570944]  [MGI Ref ID J:167036]

Additional References

Il2rgtm1Wjl related

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Covassin L; Laning J; Abdi R; Langevin DL; Phillips NE; Shultz LD; Brehm MA. 2011. Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rgamma(null) H2-Ab1 (tm1Gru) Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease. Clin Exp Immunol 166(2):269-80. [PubMed: 21985373]  [MGI Ref ID J:177904]

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Danner R; Chaudhari SN; Rosenberger J; Surls J; Richie TL; Brumeanu TD; Casares S. 2011. Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice Is Critical for Development and Function of Human T and B Cells. PLoS One 6(5):e19826. [PubMed: 21611197]  [MGI Ref ID J:172588]

Darabi R; Gehlbach K; Bachoo RM; Kamath S; Osawa M; Kamm KE; Kyba M; Perlingeiro RC. 2008. Functional skeletal muscle regeneration from differentiating embryonic stem cells. Nat Med 14(2):134-43. [PubMed: 18204461]  [MGI Ref ID J:133565]

Das R; Bassiri H; Guan P; Wiener S; Banerjee PP; Zhong MC; Veillette A; Orange JS; Nichols KE. 2013. The adaptor molecule SAP plays essential roles during invariant NKT cell cytotoxicity and lytic synapse formation. Blood 121(17):3386-95. [PubMed: 23430111]  [MGI Ref ID J:196692]

Davies E; Reid S; Medina MF; Lichty B; Ashkar AA. 2010. IL-15 has innate anti-tumor activity independent of NK and CD8 T cells. J Leukoc Biol 88(3):529-36. [PubMed: 20538758]  [MGI Ref ID J:164922]

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Dreyer AM; Matile H; Papastogiannidis P; Kamber J; Favuzza P; Voss TS; Wittlin S; Pluschke G. 2012. Passive immunoprotection of Plasmodium falciparum-infected mice designates the CyRPA as candidate malaria vaccine antigen. J Immunol 188(12):6225-37. [PubMed: 22593616]  [MGI Ref ID J:188965]

Eidenschenk C; Crozat K; Krebs P; Arens R; Popkin D; Arnold CN; Blasius AL; Benedict CA; Moresco EM; Xia Y; Beutler B. 2010. Flt3 permits survival during infection by rendering dendritic cells competent to activate NK cells. Proc Natl Acad Sci U S A :. [PubMed: 20457904]  [MGI Ref ID J:159599]

Eisenring M; vom Berg J; Kristiansen G; Saller E; Becher B. 2010. IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46. Nat Immunol 11(11):1030-8. [PubMed: 20935648]  [MGI Ref ID J:166535]

El Haddad N; Heathcote D; Moore R; Yang S; Azzi J; Mfarrej B; Atkinson M; Sayegh MH; Lee JS; Ashton-Rickardt PG; Abdi R. 2011. Mesenchymal stem cells express serine protease inhibitor to evade the host immune response. Blood 117(4):1176-83. [PubMed: 21076046]  [MGI Ref ID J:168605]

Enquist IB; Good Z; Jubb AM; Fuh G; Wang X; Junttila MR; Jackson EL; Leong KG. 2014. Lymph node-independent liver metastasis in a model of metastatic colorectal cancer. Nat Commun 5:3530. [PubMed: 24667486]  [MGI Ref ID J:210473]

Fang R; Ismail N; Walker DH. 2012. Contribution of NK cells to the innate phase of host protection against an intracellular bacterium targeting systemic endothelium. Am J Pathol 181(1):185-95. [PubMed: 22617213]  [MGI Ref ID J:185539]

Feng CG; Kaviratne M; Rothfuchs AG; Cheever A; Hieny S; Young HA; Wynn TA; Sher A. 2006. NK cell-derived IFN-gamma differentially regulates innate resistance and neutrophil response in T cell-deficient hosts infected with Mycobacterium tuberculosis. J Immunol 177(10):7086-93. [PubMed: 17082625]  [MGI Ref ID J:140483]

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Ins2Akita related

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryThe 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.
Mating SystemHOM WILD HOM X HOM HET HEMI

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00MaleHomozygous for Rag1tm1Mom, Heterozygous for Ins2Akita, Hemizygous for Il2rgtm1Wjl  
$239.00FemaleHomozygous for Rag1tm1Mom, Heterozygous for Ins2Akita, Homozygous for Il2rgtm1Wjl  
Individual Mouse $239.00MaleHomozygous for Rag1tm1Mom, Wild-type for Ins2Akita, Hemizygous for Il2rgtm1Wjl  
$239.00FemaleHomozygous for Rag1tm1Mom, Wild-type for Ins2Akita, Homozygous for Il2rgtm1Wjl  
Price per Pair (US dollars $)Pair Genotype
$478.00Homozygous for Rag1tm1Mom, Wild-type for Ins2Akita, Homozygous for Il2rgtm1Wjl x Homozygous for Rag1tm1Mom, Heterozygous for Ins2Akita, Hemizygous for Il2rgtm1Wjl  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70MaleHomozygous for Rag1tm1Mom, Heterozygous for Ins2Akita, Hemizygous for Il2rgtm1Wjl  
$310.70FemaleHomozygous for Rag1tm1Mom, Heterozygous for Ins2Akita, Homozygous for Il2rgtm1Wjl  
Individual Mouse $310.70MaleHomozygous for Rag1tm1Mom, Wild-type for Ins2Akita, Hemizygous for Il2rgtm1Wjl  
$310.70FemaleHomozygous for Rag1tm1Mom, Wild-type for Ins2Akita, Homozygous for Il2rgtm1Wjl  
Price per Pair (US dollars $)Pair Genotype
$621.40Homozygous for Rag1tm1Mom, Wild-type for Ins2Akita, Homozygous for Il2rgtm1Wjl x Homozygous for Rag1tm1Mom, Heterozygous for Ins2Akita, Hemizygous for Il2rgtm1Wjl  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   003729 NOD.129S7(B6)-Rag1tm1Mom/J (approximate) NOD.129S7(B6)-Rag1tm1Mom/J (Stock No. 003729) may be an appropriate experimental control strain.
   007799 NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (approximate) NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (Stock No. 007799) may be an appropriate experimental control strain.
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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.


See Terms of Use tab for General Terms and Conditions


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.
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Terms of Use

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General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Research institutions require an MTA, companies require a license prior to shipping.

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phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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