Strain Name:

NOD.129S2(B6)-Cd28tm1Mak/JbsJ

Stock Number:

004761

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
H2 Haplotypeg7
 
Donating InvestigatorDr. Jeffrey A. Bluestone,   University of California, San Francisco

Appearance
albino, pink-eyed
Related Genotype: A/A Tyrc/Tyrc

Description
NOD mice heterozygous for the Cd28tm1Mak mutation are viable, fertile; exhibiting diabetes onset and incidence similar to NOD. NOD mice homozygous for Cd28tm1Mak experience rapid onset Type 1 diabetes in both males and females. When stimulated with anti-Cd3 mAB, T cells from CD28 deficient NOD mice proliferate poorly when compared with wildtype controls. Nor do T cells proliferate in culture after the mice have been immunized with ovalbumin (OVA) in complete Freundís adjuvant. The IL-2 level of T-cells from mice that have been stimulated with either anti-Cd3 or OVA was significantly reduced. However, when challenged with GAD the CD28 deficient mice produced normal levels of IL-2. RT-PCR indicates a dramatic increase in the amount of IFNgamma and decreased IL4 compared to heterozygous controls. 1.5% of CD4 T cells from homozygous mice express CD25, while 6.5% of the CD4 T cells express CD25 in their wildtype cohorts.

This model is useful for studying the CTLA4/CD28:CD80/CD86 pathways in the regulation of self tolerance and susceptibility to autoimmune diseases.

Development
Cd28, located on Chr. 1, 30.1cM, is involved in costimulatory signaling important for T cell activation. A construct containing a neomycin expression cassette replacing part of exon 2 of Cd28 was transfected into D3 (129S2/SvPas derived) embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. As reported by Lenschow et al 1996, chimeric founders were initially mated to C57BL/6 and intercrossed to generate Cd28 deficient mice. B6 congenic mice homozygous for the mutation were subsequently mated to NOD for 4 generations, Lenschow et al 1996, prior to making homozygous. In 2006, the T1DR received mice heterozygous for the mutation at generation N11.

Control Information

  Control
   Wild-type from the colony
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Cd28tm1Mak allele
002666   B6.129S2-Cd28tm1Mak/J
002667   C.129S2(B6)-Cd28tm1Mak/J
View Strains carrying   Cd28tm1Mak     (2 strains)

Strains carrying other alleles of Cd28
017607   B6.129S4-Cd28tm1Shr Ctla4tm1Shr/J
012302   B6.129X1-Cd28tm1Jmg/Mmjax
012305   B6.129X1-Cd28tm2.1Jmg/Mmjax
024282   C57BL/6-Cd28tm1Ltu/J
View Strains carrying other alleles of Cd28     (4 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Cd28tm1Mak/Cd28tm1Mak

        NOD.129S2-Cd28tm1Mak
  • immune system phenotype
  • abnormal CD4-positive T cell physiology
    • only 1.5% of CD4 T cells in homozygotes express CD25 compared to 6.5% in wild-type   (MGI Ref ID J:61905)
  • abnormal response to transplant
    • CD28-deficient NOD mice injected with CD4+CD25+ NOD T cells showed significant delay in the development of diabetes with no disease apparent through 15 weeks of age, whereas transfer of CD4+CD25+ T cells resulted in diabetes development by 11 weeks of age   (MGI Ref ID J:61905)
  • increased T cell proliferation
    • expansion of transferred CD25-depleted T cells from Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi is dramatically accelerated compared to NOD controls; there are 5-fold more autoreactive transferred T cells in pancreatic lymph nodes compared to NOD mice   (MGI Ref ID J:93421)
  • increased susceptibility to autoimmune diabetes
    • mice show higher incidence of diabetes compared to Cd40lg, Cd28 double null mice   (MGI Ref ID J:93421)
  • hematopoietic system phenotype
  • abnormal CD4-positive T cell physiology
    • only 1.5% of CD4 T cells in homozygotes express CD25 compared to 6.5% in wild-type   (MGI Ref ID J:61905)
  • increased T cell proliferation
    • expansion of transferred CD25-depleted T cells from Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi is dramatically accelerated compared to NOD controls; there are 5-fold more autoreactive transferred T cells in pancreatic lymph nodes compared to NOD mice   (MGI Ref ID J:93421)

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Cd28tm1Mak/Cd28tm1Mak

        involves: 129S2/SvPas * NOD
  • immune system phenotype
  • abnormal T-helper 1 physiology
    • Th1 responses are enhanced in these mice   (MGI Ref ID J:35353)
    • splenic T cells secrete high levels of IFN-gamma while expressing very little to no IL-4 upon stimulation   (MGI Ref ID J:35353)
  • abnormal T-helper 2 physiology
    • Th2 responses are dampened in these mice   (MGI Ref ID J:35353)
    • splenic T cells secrete high levels of IFN-gamma while expressing very little to no IL-4 upon stimulation   (MGI Ref ID J:35353)
    • serum contains significantly less of the Th2-dependent anti-GAD IgG2a antibodies   (MGI Ref ID J:35353)
  • decreased IgG2a level
    • serum contains significantly less of the Th2-dependent anti-GAD IgG2a antibodies   (MGI Ref ID J:35353)
  • decreased T cell proliferation
    • T cells stimulated in vitro proliferate much less than controls to anti-CD3   (MGI Ref ID J:35353)
    • T cells fail to proliferate when restimulated with OVA peptide   (MGI Ref ID J:35353)
    • T cells also produce less IL-2 during these in vitro stimulations   (MGI Ref ID J:35353)
  • decreased interleukin-2 secretion
    • T cells also produce less IL-2 during stimulation with anti-CD3 antibody or upon restimulation with OVA peptide   (MGI Ref ID J:35353)
    • T cells secrete the same amout of IL-2 as controls when stimulated with the diabetic autoantigen GAD   (MGI Ref ID J:35353)
  • decreased interleukin-4 secretion
    • T cell secrete little to no IL-4 upon activation in vitro   (MGI Ref ID J:35353)
  • increased interferon-gamma secretion
    • splenic T cells secrete high levels of IFN-gamma, sometimes as much as 4-fold compared to controls   (MGI Ref ID J:35353)
  • increased susceptibility to autoimmune diabetes
    • 70-80% of female mice in the fourth backcross onto the NOD strain are hyperglycemic by 24 weeks of age compared to 30% for non-transgenic littermate controls   (MGI Ref ID J:35353)
    • nearly 90% of male mice in this backcross are hyperglycemic by 24 weeks of age compared to 10% of non-transgenic littermate controls   (MGI Ref ID J:35353)
  • hematopoietic system phenotype
  • abnormal T-helper 1 physiology
    • Th1 responses are enhanced in these mice   (MGI Ref ID J:35353)
    • splenic T cells secrete high levels of IFN-gamma while expressing very little to no IL-4 upon stimulation   (MGI Ref ID J:35353)
  • abnormal T-helper 2 physiology
    • Th2 responses are dampened in these mice   (MGI Ref ID J:35353)
    • splenic T cells secrete high levels of IFN-gamma while expressing very little to no IL-4 upon stimulation   (MGI Ref ID J:35353)
    • serum contains significantly less of the Th2-dependent anti-GAD IgG2a antibodies   (MGI Ref ID J:35353)
  • decreased IgG2a level
    • serum contains significantly less of the Th2-dependent anti-GAD IgG2a antibodies   (MGI Ref ID J:35353)
  • decreased T cell proliferation
    • T cells stimulated in vitro proliferate much less than controls to anti-CD3   (MGI Ref ID J:35353)
    • T cells fail to proliferate when restimulated with OVA peptide   (MGI Ref ID J:35353)
    • T cells also produce less IL-2 during these in vitro stimulations   (MGI Ref ID J:35353)
View Research Applications

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

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Cd28tm1Mak related

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Cd28tm1Mak
Allele Name targeted mutation 1, Tak Mak
Allele Type Targeted (knock-out)
Common Name(s) CD28-; CD28KO;
Mutation Made ByDr. Tak Mak,   University Health Network/Un of Toronto
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Cd28, CD28 antigen
Chromosome 1
Gene Common Name(s) CD28RNA; Tp44;
Molecular Note A genomic fragment containing part of exon 2 was replaced by a neomycin resistance cassette. Flow-cytometry analysis on peripheral blood lymphocytes demonstrated that the protein was not expressed in these cells in homozygous mice. [MGI Ref ID J:14194]

Genotyping

Genotyping Information

Genotyping Protocols

Cd28tm1Makalternate1, Separated PCR
Cd28tm1Mak, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Salomon B; Lenschow DJ; Rhee L; Ashourian N; Singh B; Sharpe A; Bluestone JA. 2000. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12(4):431-40. [PubMed: 10795741]  [MGI Ref ID J:61905]

Shahinian A; Pfeffer K; Lee KP; Kundig TM; Kishihara K; Wakeham A; Kawai K; Ohashi PS; Thompson CB; Mak TW. 1993. Differential T cell costimulatory requirements in CD28-deficient mice. Science 261(5121):609-12. [PubMed: 7688139]  [MGI Ref ID J:14194]

Cd28tm1Mak related

Ait-Oufella H; Salomon BL; Potteaux S; Robertson AK; Gourdy P; Zoll J; Merval R; Esposito B; Cohen JL; Fisson S; Flavell RA; Hansson GK; Klatzmann D; Tedgui A; Mallat Z. 2006. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12(2):178-80. [PubMed: 16462800]  [MGI Ref ID J:105800]

Akbari O; Stock P; Meyer EH; Freeman GJ; Sharpe AH; Umetsu DT; DeKruyff RH. 2008. ICOS/ICOSL interaction is required for CD4+ invariant NKT cell function and homeostatic survival. J Immunol 180(8):5448-56. [PubMed: 18390727]  [MGI Ref ID J:134254]

Akiba H; Takeda K; Kojima Y; Usui Y; Harada N; Yamazaki T; Ma J; Tezuka K; Yagita H; Okumura K. 2005. The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo. J Immunol 175(4):2340-8. [PubMed: 16081804]  [MGI Ref ID J:107507]

Alegre ML; Shiels H; Thompson CB; Gajewski TF. 1998. Expression and function of CTLA-4 in Th1 and Th2 cells. J Immunol 161(7):3347-56. [PubMed: 9759851]  [MGI Ref ID J:115196]

Ali M; Weinreich M; Balcaitis S; Cooper CJ; Fink PJ. 2003. Differential regulation of peripheral CD4+ T cell tolerance induced by deletion and TCR revision. J Immunol 171(11):6290-6. [PubMed: 14634147]  [MGI Ref ID J:132828]

Andreasen SO; Christensen JE; Marker O; Thomsen AR. 2000. Role of CD40 ligand and CD28 in induction and maintenance of antiviral CD8+ effector T cell responses. J Immunol 164(7):3689-97. [PubMed: 10725727]  [MGI Ref ID J:123023]

Arens R; Loewendorf A; Redeker A; Sierro S; Boon L; Klenerman P; Benedict CA; Schoenberger SP. 2011. Differential B7-CD28 Costimulatory Requirements for Stable and Inflationary Mouse Cytomegalovirus-Specific Memory CD8 T Cell Populations. J Immunol 186(7):3874-81. [PubMed: 21357256]  [MGI Ref ID J:170700]

Arimura Y; Ezaki T; Koyanagi M; Uchiyama T; Koyasu S; Yagi J. 2010. Reduced T cell expansion by a superantigen as a result of impaired B cell development in mice deficient for the p85alpha regulatory subunit of PI3K. J Leukoc Biol 87(3):493-500. [PubMed: 20007249]  [MGI Ref ID J:158856]

Arjunaraja S; Massari P; Wetzler LM; Lees A; Colino J; Snapper CM. 2012. The nature of an in vivo anti-capsular polysaccharide response is markedly influenced by the composition and/or architecture of the bacterial subcapsular domain. J Immunol 188(2):569-77. [PubMed: 22156342]  [MGI Ref ID J:180885]

Asai T; Choi BK; Kwon PM; Kim WY; Kim JD; Vinay DS; Gebhardt BM; Kwon BS. 2007. Blockade of the 4-1BB (CD137)/4-1BBL and/or CD28/CD80/CD86 costimulatory pathways promotes corneal allograft survival in mice. Immunology 121(3):349-58. [PubMed: 17376197]  [MGI Ref ID J:125540]

Aumeunier A; Grela F; Ramadan A; Pham Van L; Bardel E; Gomez Alcala A; Jeannin P; Akira S; Bach JF; Thieblemont N. 2010. Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice. PLoS One 5(7):e11484. [PubMed: 20628601]  [MGI Ref ID J:163119]

Bai XF; Liu JQ; Liu X; Guo Y; Cox K; Wen J; Zheng P; Liu Y. 2000. The heat-stable antigen determines pathogenicity of self-reactive T cells in experimental autoimmune encephalomyelitis. J Clin Invest 105(9):1227-32. [PubMed: 10791997]  [MGI Ref ID J:120498]

Beck JM; Blackmon MB; Rose CM; Kimzey SL; Preston AM; Green JM. 2003. T cell costimulatory molecule function determines susceptibility to infection with Pneumocystis carinii in mice. J Immunol 171(4):1969-77. [PubMed: 12902500]  [MGI Ref ID J:121189]

Belghith M; Bluestone JA; Barriot S; Megret J; Bach JF; Chatenoud L. 2003. TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat Med 9(9):1202-8. [PubMed: 12937416]  [MGI Ref ID J:85362]

Berg-Brown NN; Gronski MA; Jones RG; Elford AR; Deenick EK; Odermatt B; Littman DR; Ohashi PS. 2004. PKCtheta signals activation versus tolerance in vivo. J Exp Med 199(6):743-52. [PubMed: 15024044]  [MGI Ref ID J:123989]

Bergqvist P; Gardby E; Stensson A; Bemark M; Lycke NY. 2006. Gut IgA class switch recombination in the absence of CD40 does not occur in the lamina propria and is independent of germinal centers. J Immunol 177(11):7772-83. [PubMed: 17114448]  [MGI Ref ID J:140700]

Bertram EM; Lau P; Watts TH. 2002. Temporal Segregation of 4-1BB Versus CD28-Mediated Costimulation: 4-1BB Ligand Influences T Cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory Response Following Influenza Infection. J Immunol 168(8):3777-85. [PubMed: 11937529]  [MGI Ref ID J:75925]

Bertram EM; Tafuri A; Shahinian A; Chan VS; Hunziker L; Recher M; Ohashi PS; Mak TW; Watts TH. 2002. Role of ICOS versus CD28 in antiviral immunity. Eur J Immunol 32(12):3376-85. [PubMed: 12432568]  [MGI Ref ID J:80851]

Bhatia S; Sun K; Almo SC; Nathenson SG; Hodes RJ. 2010. Dynamic equilibrium of B7-1 dimers and monomers differentially affects immunological synapse formation and T cell activation in response to TCR/CD28 stimulation. J Immunol 184(4):1821-8. [PubMed: 20065109]  [MGI Ref ID J:159491]

Blazar BR; Lees CJ; Martin PJ; Noelle RJ; Kwon B; Murphy W; Taylor PA. 2000. Host T cells resist graft-versus-host disease mediated by donor leukocyte infusions. J Immunol 165(9):4901-9. [PubMed: 11046015]  [MGI Ref ID J:118027]

Boenisch O; D'Addio F; Watanabe T; Elyaman W; Magee CN; Yeung MY; Padera RF; Rodig SJ; Murayama T; Tanaka K; Yuan X; Ueno T; Jurisch A; Mfarrej B; Akiba H; Yagita H; Najafian N. 2010. TIM-3: a novel regulatory molecule of alloimmune activation. J Immunol 185(10):5806-19. [PubMed: 20956339]  [MGI Ref ID J:165781]

Boone DL; Dassopoulos T; Lodolce JP; Chai S; Chien M; Ma A. 2002. Interleukin-2-deficient mice develop colitis in the absence of CD28 costimulation. Inflamm Bowel Dis 8(1):35-42. [PubMed: 11837936]  [MGI Ref ID J:113015]

Bour-Jordan H; Salomon BL; Thompson HL; Santos R; Abbas AK; Bluestone JA. 2007. Constitutive expression of B7-1 on B cells uncovers autoimmunity toward the B cell compartment in the nonobese diabetic mouse. J Immunol 179(2):1004-12. [PubMed: 17617592]  [MGI Ref ID J:131077]

Bour-Jordan H; Salomon BL; Thompson HL; Szot GL; Bernhard MR; Bluestone JA. 2004. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J Clin Invest 114(7):979-87. [PubMed: 15467837]  [MGI Ref ID J:93421]

Bry L; Brigl M; Brenner MB. 2006. CD4+-T-cell effector functions and costimulatory requirements essential for surviving mucosal infection with Citrobacter rodentium. Infect Immun 74(1):673-81. [PubMed: 16369024]  [MGI Ref ID J:104251]

Buhlmann JE; Elkin SK; Sharpe AH. 2003. A Role for the B7-1/B7-2:CD28/CTLA-4 Pathway During Negative Selection. J Immunol 170(11):5421-8. [PubMed: 12759417]  [MGI Ref ID J:83454]

Burne MJ; Daniels F; El Ghandour A; Mauiyyedi S; Colvin RB; O'Donnell MP; Rabb H. 2001. Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure. J Clin Invest 108(9):1283-90. [PubMed: 11696572]  [MGI Ref ID J:118005]

Burr JS; Kimzey SL; Randolph DR; Green JM. 2001. CD28 and CTLA4 coordinately regulate airway inflammatory cell recruitment and T-helper cell differentiation after inhaled allergen. Am J Respir Cell Mol Biol 24(5):563-8. [PubMed: 11350825]  [MGI Ref ID J:114405]

Byrum JN; Van Komen JS; Rodgers W. 2013. CD28 sensitizes TCR Ca(2)(+) signaling during Ag-independent polarization of plasma membrane rafts. J Immunol 191(6):3073-81. [PubMed: 23966623]  [MGI Ref ID J:205860]

Calzascia T; Pellegrini M; Lin A; Garza KM; Elford AR; Shahinian A; Ohashi PS; Mak TW. 2008. CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity. Proc Natl Acad Sci U S A 105(8):2999-3004. [PubMed: 18287017]  [MGI Ref ID J:132821]

Cannons JL; Choi Y; Watts TH. 2000. Role of TNF receptor-associated factor 2 and p38 mitogen-activated protein kinase activation during 4-1BB-dependent immune response. J Immunol 165(11):6193-204. [PubMed: 11086053]  [MGI Ref ID J:118025]

Cawthon AG; Kroger CJ; Alexander-Miller MA. 2004. High avidity CD8+ T cells generated from CD28-deficient or wildtype mice exhibit a differential dependence on lipid raft integrity for activation. Cell Immunol 227(2):148-55. [PubMed: 15135297]  [MGI Ref ID J:89576]

Chakravarti S; Hassell JR. 1991. Assignment of the gene for perlecan to mouse chromosome 4 Am J Hum Genet 49 (suppl):338 (Abstr.).  [MGI Ref ID J:12098]

Chang TT; Jabs C; Sobel RA; Kuchroo VK; Sharpe AH. 1999. Studies in B7-deficient mice reveal a critical role for B7 costimulation in both induction and effector phases of experimental autoimmune encephalomyelitis. J Exp Med 190(5):733-40. [PubMed: 10477557]  [MGI Ref ID J:57613]

Chapoval SP; David CS. 2003. CD28 costimulation is critical for experimental allergic asthma in HLA-DQ8 transgenic mice. Clin Immunol 106(2):83-94. [PubMed: 12672399]  [MGI Ref ID J:82789]

Chen L; Cheng W; Shivshankar P; Lei L; Zhang X; Wu Y; Yeh IT; Zhong G. 2009. Distinct roles of CD28- and CD40 ligand-mediated costimulation in the development of protective immunity and pathology during Chlamydia muridarum urogenital infection in mice. Infect Immun 77(7):3080-9. [PubMed: 19398542]  [MGI Ref ID J:150306]

Chen Q; Cannons JL; Paton JC; Akiba H; Schwartzberg PL; Snapper CM. 2008. A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine. J Immunol 181(12):8258-66. [PubMed: 19050242]  [MGI Ref ID J:142078]

Chen Y; Shen S; Gorentla BK; Gao J; Zhong XP. 2012. Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression. J Immunol 188(4):1698-707. [PubMed: 22231701]  [MGI Ref ID J:181206]

Chitnis T; Najafian N; Abdallah KA; Dong V; Yagita H; Sayegh MH; Khoury SJ. 2001. CD28-independent induction of experimental autoimmune encephalomyelitis. J Clin Invest 107(5):575-83. [PubMed: 11238558]  [MGI Ref ID J:120551]

Cho JH; Kim HO; Surh CD; Sprent J. 2010. T cell receptor-dependent regulation of lipid rafts controls naive CD8+ T cell homeostasis. Immunity 32(2):214-26. [PubMed: 20137986]  [MGI Ref ID J:157928]

Christensen JE; Christensen JP; Kristensen NN; Hansen NJ; Stryhn A; Thomsen AR. 2002. Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells. Int Immunol 14(7):701-11. [PubMed: 12096029]  [MGI Ref ID J:113535]

Chung DR; Kasper DL; Panzo RJ; Chtinis T; Grusby MJ; Sayegh MH; Tzianabos AO. 2003. CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J Immunol 170(4):1958-63. [PubMed: 12574364]  [MGI Ref ID J:81809]

Chung Y; Nurieva R; Esashi E; Wang YH; Zhou D; Gapin L; Dong C. 2008. A critical role of costimulation during intrathymic development of invariant NK T cells. J Immunol 180(4):2276-83. [PubMed: 18250436]  [MGI Ref ID J:131999]

Compton HL; Farrell JP. 2002. CD28 costimulation and parasite dose combine to influence the susceptibility of BALB/c mice to infection with Leishmania major. J Immunol 168(3):1302-8. [PubMed: 11801669]  [MGI Ref ID J:127289]

Dautigny N; Le Campion A; Lucas B. 1999. Timing and casting for actors of thymic negative selection. J Immunol 162(3):1294-302. [PubMed: 9973382]  [MGI Ref ID J:124433]

DeBenedette MA; Wen T; Bachmann MF; Ohashi PS; Barber BH; Stocking KL; Peschon JJ; Watts TH. 1999. Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus. J Immunol 163(9):4833-41. [PubMed: 10528184]  [MGI Ref ID J:76373]

Delogu A; Schebesta A; Sun Q; Aschenbrenner K; Perlot T; Busslinger M. 2006. Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells. Immunity 24(3):269-81. [PubMed: 16546096]  [MGI Ref ID J:113322]

Demirci G; Amanullah F; Kewalaramani R; Yagita H; Strom TB; Sayegh MH; Li XC. 2004. Critical role of OX40 in CD28 and CD154-independent rejection. J Immunol 172(3):1691-8. [PubMed: 14734751]  [MGI Ref ID J:87657]

Dodson LF; Boomer JS; Deppong CM; Shah DD; Sim J; Bricker TL; Russell JH; Green JM. 2009. Targeted knock-in mice expressing mutations of CD28 reveal an essential pathway for costimulation. Mol Cell Biol 29(13):3710-21. [PubMed: 19398586]  [MGI Ref ID J:149888]

Ekkens MJ; Liu Z; Liu Q; Foster A; Whitmire J; Pesce J; Sharpe AH; Urban JF; Gause WC. 2002. Memory Th2 effector cells can develop in the absence of B7-1/B7-2, CD28 interactions, and effector Th cells after priming with an intestinal nematode parasite. J Immunol 168(12):6344-51. [PubMed: 12055251]  [MGI Ref ID J:123794]

Elias RM; Sardinha LR; Bastos KR; Zago CA; da Silva AP; Alvarez JM; Lima MR. 2005. Role of CD28 in polyclonal and specific T and B cell responses required for protection against blood stage malaria. J Immunol 174(2):790-9. [PubMed: 15634900]  [MGI Ref ID J:95837]

Ellyard JI; Chia T; Rodriguez-Pinilla SM; Martin JL; Hu X; Navarro-Gonzalez M; Garcia JF; Delfau-Larue MH; Montes-Moreno S; Gaulard P; Cook MC; Walters G; Piris MA; Vinuesa CG. 2012. Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice. Blood 120(4):812-21. [PubMed: 22700722]  [MGI Ref ID J:189087]

Fallarino F; Fields PE; Gajewski TF. 1998. B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28. J Exp Med 188(1):205-10. [PubMed: 9653097]  [MGI Ref ID J:111538]

Fang D; Liu YC. 2001. Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol 2(9):870-5. [PubMed: 11526404]  [MGI Ref ID J:125680]

Ferguson SE; Han S; Kelsoe G; Thompson CB. 1996. CD28 is required for germinal center formation. J Immunol 156(12):4576-81. [PubMed: 8648099]  [MGI Ref ID J:110668]

Fischbein MP; Ardehali A; Yun J; Schoenberger S; Laks H; Irie Y; Dempsey P; Cheng G; Fishbein MC; Bonavida B. 2000. CD40 signaling replaces CD4+ lymphocytes and its blocking prevents chronic rejection of heart transplants. J Immunol 165(12):7316-22. [PubMed: 11120867]  [MGI Ref ID J:118395]

Flano E; Husain SM; Sample JT; Woodland DL; Blackman MA. 2000. Latent murine gamma-herpesvirus infection is established in activated B cells, dendritic cells, and macrophages. J Immunol 165(2):1074-81. [PubMed: 10878386]  [MGI Ref ID J:120495]

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Walunas TL; Lenschow DJ; Bakker CY; Linsley PS; Freeman GJ; Green JM; Thompson CB; Bluestone JA. 1994. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1(5):405-13. [PubMed: 7882171]  [MGI Ref ID J:189426]

Wen T; Kono K; Shahinian A; Kiessling R; Mak TW; Klein G. 1997. CD28 is not required for rejection of unmanipulated syngeneic and autologous tumors. Eur J Immunol 27(8):1988-93. [PubMed: 9295036]  [MGI Ref ID J:42096]

Wiest DL; Ashe JM; Howcroft TK; Lee HM; Kemper DM; Negishi I ; Singer DS ; Singer A ; Abe R. 1997. A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development. Immunity 6(6):663-71. [PubMed: 9208839]  [MGI Ref ID J:41170]

Williams CA; Murray SE; Weinberg AD; Parker DC. 2007. OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rbeta2, or T-bet. J Immunol 178(12):7694-702. [PubMed: 17548606]  [MGI Ref ID J:148588]

Williams JA; Lumsden JM; Yu X; Feigenbaum L; Zhang J; Steinberg SM; Hodes RJ. 2008. Regulation of thymic NKT cell development by the B7-CD28 costimulatory pathway. J Immunol 181(2):907-17. [PubMed: 18606642]  [MGI Ref ID J:137437]

Williams JA; Sharrow SO; Adams AJ; Hodes RJ. 2002. CD40 ligand functions non-cell autonomously to promote deletion of self-reactive thymocytes. J Immunol 168(6):2759-65. [PubMed: 11884443]  [MGI Ref ID J:126679]

Wohlfert EA; Gorelik L; Mittler R; Flavell RA; Clark RB. 2006. Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results in a multifunctional defect in T cell TGF-beta sensitivity in vitro and in vivo. J Immunol 176(3):1316-20. [PubMed: 16424156]  [MGI Ref ID J:126434]

Wolfraim LA; Letterio JJ. 2005. Cutting edge: p27Kip1 deficiency reduces the requirement for CD28-mediated costimulation in naive CD8+ but not CD4+ T lymphocytes. J Immunol 174(5):2481-4. [PubMed: 15728451]  [MGI Ref ID J:97741]

Wong SC; Tan AH; Lam KP. 2009. Functional hierarchy and relative contribution of the CD28/B7 and ICOS/B7-H2 costimulatory pathways to T cell-mediated delayed-type hypersensitivity. Cell Immunol 256(1-2):64-71. [PubMed: 19249753]  [MGI Ref ID J:148551]

Wu Y; Zhou Q; Zheng P; Liu Y. 1998. CD28-independent induction of T helper cells and immunoglobulin class switches requires costimulation by the heat-stable antigen. J Exp Med 187(7):1151-6. [PubMed: 9529332]  [MGI Ref ID J:76971]

Wu ZQ; Khan AQ; Shen Y; Schartman J; Peach R; Lees A; Mond JJ; Gause WC; Snapper CM. 2000. B7 requirements for primary and secondary protein- and polysaccharide-specific Ig isotype responses to Streptococcus pneumoniae. J Immunol 165(12):6840-8. [PubMed: 11120807]  [MGI Ref ID J:118398]

Xiao Y; Hendriks J; Langerak P; Jacobs H; Borst J. 2004. CD27 is acquired by primed B cells at the centroblast stage and promotes germinal center formation. J Immunol 172(12):7432-41. [PubMed: 15187121]  [MGI Ref ID J:90837]

Yamada A; Salama AD; Sho M; Najafian N; Ito T; Forman JP; Kewalramani R; Sandner S; Harada H; Clarkson MR; Mandelbrot DA; Sharpe AH; Oshima H; Yagita H; Chalasani G; Lakkis FG; Auchincloss H Jr; Sayegh MH. 2005. CD70 signaling is critical for CD28-independent CD8+ T cell-mediated alloimmune responses in vivo. J Immunol 174(3):1357-64. [PubMed: 15661893]  [MGI Ref ID J:136519]

Yamaguchi T; Kishi A; Osaki M; Morikawa H; Prieto-Martin P; Wing K; Saito T; Sakaguchi S. 2013. Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression. Proc Natl Acad Sci U S A 110(23):E2116-25. [PubMed: 23690575]  [MGI Ref ID J:197416]

Yao S; Zhu Y; Zhu G; Augustine M; Zheng L; Goode DJ; Broadwater M; Ruff W; Flies S; Xu H; Flies D; Luo L; Wang S; Chen L. 2011. B7-h2 is a costimulatory ligand for CD28 in human. Immunity 34(5):729-40. [PubMed: 21530327]  [MGI Ref ID J:172609]

Yin D; Zhang L; Wang R; Radvanyi L; Haudenschild C; Fang Q; Kehry MR; Shi Y. 1999. Ligation of CD28 in vivo induces CD40 ligand expression and promotes B cell survival. J Immunol 163(8):4328-34. [PubMed: 10510372]  [MGI Ref ID J:119231]

Ying H; Yang L; Qiao G; Li Z; Zhang L; Yin F; Xie D; Zhang J. 2010. Cutting edge: CTLA-4-B7 interaction suppresses Th17 cell differentiation. J Immunol 185(3):1375-8. [PubMed: 20601598]  [MGI Ref ID J:162452]

Yokosuka T; Kobayashi W; Takamatsu M; Sakata-Sogawa K; Zeng H; Hashimoto-Tane A; Yagita H; Tokunaga M; Saito T. 2010. Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation. Immunity 33(3):326-39. [PubMed: 20870175]  [MGI Ref ID J:164647]

Yu D. 2007. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA Nature 450:299-304.  [MGI Ref ID J:127784]

Yu X; Fournier S; Allison JP; Sharpe AH; Hodes RJ. 2000. The role of B7 costimulation in CD4/CD8 T cell homeostasis. J Immunol 164(7):3543-53. [PubMed: 10725709]  [MGI Ref ID J:112266]

Yu XZ; Liang Y; Nurieva RI; Guo F; Anasetti C; Dong C. 2006. Opposing effects of ICOS on graft-versus-host disease mediated by CD4 and CD8 T cells. J Immunol 176(12):7394-401. [PubMed: 16751384]  [MGI Ref ID J:132339]

Zehntner SP; Brisebois M; Tran E; Owens T; Fournier S. 2003. Constitutive expression of a costimulatory ligand on antigen-presenting cells in the nervous system drives demyelinating disease. FASEB J 17(13):1910-2. [PubMed: 12923072]  [MGI Ref ID J:127902]

Zhang J; Bardos T; Li D; Gal I; Vermes C; Xu J; Mikecz K; Finnegan A; Lipkowitz S; Glant TT. 2002. Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. J Immunol 169(5):2236-40. [PubMed: 12193687]  [MGI Ref ID J:120676]

Zheng X; Gao JX; Chang X; Wang Y; Liu Y; Wen J; Zhang H; Zhang J; Liu Y; Zheng P. 2004. B7-CD28 interaction promotes proliferation and survival but suppresses differentiation of CD4-CD8- T cells in the thymus. J Immunol 173(4):2253-61. [PubMed: 15294937]  [MGI Ref ID J:92731]

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Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, heterozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

General Supply Notes

Control Information

  Control
   Wild-type from the colony
   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

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires 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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