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. Species laboratory mouse Background Strain BALB/c Donor Strain B6;129S-Cd28tm1Mak (129S2 derived D3 ES cell line) Generation N6F17pN1   Donating Investigator Tak Mak,   University Health Network/Un of Toronto

Appearance
albino
Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c

Description
Mice homozygous for the Cd28^tm1Mak targeted mutation exhibit normal development of T and B cells, but have an impaired response to lectins. Other characteristics of homozygous mutant mice include decreased IL2 receptor expression, reduced basal Ig levels, low titers of IgG1 and IgG2b but increased IgG2a, reduced activity of T helper cells and diminished Ig class switching after infection with vesicular stomatitis virus. Infection of mice with lymphocytic choriomeningities virus creates induced and delayed-type hypersensitivity response in cytotoxic T cells.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Cd28^tm1Mak allele

002666	B6.129S2-Cd28tm1Mak/J
004761	NOD.129S2(B6)-Cd28tm1Mak/JbsJ

View Strains carrying   Cd28^tm1Mak     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Cd28^tm1Mak/Cd28^tm1Mak

        involves: 129S2/SvPas * C57BL/6 * DBA/2

• immune system phenotype
• abnormal T cell physiology (MGI Ref ID J:14194)
  • impaired T cell response to stimulation with lectins
• abnormal CD4-positive T cell physiology (MGI Ref ID J:14194)
  • decreased T helper cell activity
• decreased immunoglobulin level (MGI Ref ID J:14194)
  • basal level of immunoglobulins is 20% that of wild-type

Cd28^tm1Mak/Cd28^tm1Mak

        involves: C57BL/6

• immune system phenotype
• abnormal NK cell physiology (MGI Ref ID J:95353)
  • alpha-galactosylceramide-induced cytotoxic activity of splenic and hepatic mononuclear cells was reduced compared to wild-type
  • alpha-galactosylceramide-induced anti-metastatic effect was substantially reduced compared to wild-type, indicating that natural killer cells are not able to fight off cancer cells
• decreased circulating interferon-gamma level (MGI Ref ID J:95353)
  • alpha-galactosylceramide-induced serum IFN-gamma levels were reduced compared to wild-type
• decreased circulating interleukin-4 level (MGI Ref ID J:95353)
  • alpha-galactosylceramide-induced (an antigen that activates invariant natural killer T cells) serum IL-4 levels were reduced compared to wild-type
• homeostasis/metabolism phenotype
• decreased circulating interferon-gamma level (MGI Ref ID J:95353)
  • alpha-galactosylceramide-induced serum IFN-gamma levels were reduced compared to wild-type
• decreased circulating interleukin-4 level (MGI Ref ID J:95353)
  • alpha-galactosylceramide-induced (an antigen that activates invariant natural killer T cells) serum IL-4 levels were reduced compared to wild-type

Cd28^tm1Mak/Cd28^tm1Mak

        involves: 129S2/SvPas

• immune system phenotype
• decreased T cell proliferation (MGI Ref ID J:130882)
  • CD4 T cells fail to proliferate in vitro when stimulated with low or high doses of anti-CD3 antibody
• decreased interleukin-2 secretion (MGI Ref ID J:130882)
  • CD4 T cells fail to secrete IL-2 upon stimulation with anti -CD3 or -CD3/-CD28 antibodies
• hematopoietic system phenotype
• decreased T cell proliferation (MGI Ref ID J:130882)
  • CD4 T cells fail to proliferate in vitro when stimulated with low or high doses of anti-CD3 antibody

View Research Applications

Research Applications

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

Cd28^tm1Mak related

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

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cd28tm1Mak
Allele Name		targeted mutation 1, Tak Mak
Allele Type		Targeted (knock-out)
Common Name(s)		CD28-; CD28KO;
Mutation Made By		Tak Mak,   University Health Network/Un of Toronto
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Cd28, CD28 antigen
Chromosome		1
Gene Common Name(s)		CD28RNA; MGC138290; 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

Cd28^tm1Mak, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

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]

Hagen KA; Moses CT; Drasler EF; Podetz-Pedersen KM; Jameson SC; Khoruts A. 2004. A role for CD28 in lymphopenia-induced proliferation of CD4 T cells. J Immunol 173(6):3909-15. [PubMed: 15356139]  [MGI Ref ID J:92743]

Kawai K; Shahinian A; Mak TW; Ohashi PS. 1996. Skin allograft rejection in CD28-deficient mice. Transplantation 61(3):352-5. [PubMed: 8610339]  [MGI Ref ID J:31421]

Mandelbrot DA; Oosterwegel MA; Shimizu K; Yamada A; Freeman GJ; Mitchell RN; Sayegh MH; Sharpe AH. 2001. B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4. J Clin Invest 107(7):881-7. [PubMed: 11285307]  [MGI Ref ID J:68642]

Mittrucker HW; Shahinian A; Bouchard D; Kundig TM; Mak TW. 1996. Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice. J Exp Med 183(6):2481-8. [PubMed: 8676068]  [MGI Ref ID J:33610]

Rogers PR; Song J; Gramaglia I; Killeen N; Croft M. 2001. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity 15(3):445-55. [PubMed: 11567634]  [MGI Ref ID J:71803]

Cd28^tm1Mak 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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

Freitas do Rosario AP; Muxel SM; Rodriguez-Malaga SM; Sardinha LR; Zago CA; Castillo-Mendez SI; Alvarez JM; D'Imperio Lima MR. 2008. Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody. J Immunol 181(12):8344-55. [PubMed: 19050251]  [MGI Ref ID J:142073]

Friend LD; Shah DD; Deppong C; Lin J; Bricker TL; Juehne TI; Rose CM; Green JM. 2006. A dose-dependent requirement for the proline motif of CD28 in cellular and humoral immunity revealed by a targeted knockin mutant. J Exp Med 203(9):2121-33. [PubMed: 16908623]  [MGI Ref ID J:124570]

Fukada K; Koyanagi M; Arimura Y; Ogiuchi H; Uchiyama T; Yagi J. 2005. CD28 is required for induction and maintenance of immunological memory in toxin-reactive CD4+ T cells in vivo. Cell Immunol 238(2):103-12. [PubMed: 16600196]  [MGI Ref ID J:108140]

Fuse S; Zhang W; Usherwood EJ. 2008. Control of memory CD8+ T cell differentiation by CD80/CD86-CD28 costimulation and restoration by IL-2 during the recall response. J Immunol 180(2):1148-57. [PubMed: 18178855]  [MGI Ref ID J:130942]

Gao JX; Chang X; Zheng X; Wen J; Yin L; Du P; Zheng P; Liu Y. 2004. A new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen. Int Immunol 16(10):1403-9. [PubMed: 15314039]  [MGI Ref ID J:93659]

Garcon F; Patton DT; Emery JL; Hirsch E; Rottapel R; Sasaki T; Okkenhaug K. 2008. CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. Blood 111(3):1464-71. [PubMed: 18006698]  [MGI Ref ID J:130753]

Gardby E; Wrammert J; Schon K; Ekman L; Leanderson T; Lycke N. 2003. Strong differential regulation of serum and mucosal IgA responses as revealed in CD28-deficient mice using cholera toxin adjuvant. J Immunol 170(1):55-63. [PubMed: 12496383]  [MGI Ref ID J:135141]

Gause WC; Chen SJ; Greenwald RJ; Halvorson MJ; Lu P; Zhou XD; Morris SC; Lee KP; June CH; Finkelman FD; Urban JF; Abe R. 1997. CD28 dependence of T cell differentiation to IL-4 production varies with the particular type 2 immune response. J Immunol 158(9):4082-7. [PubMed: 9126966]  [MGI Ref ID J:110674]

Geldhof AB; Moser M; Lespagnard L; Thielemans K; De Baetselier P. 1998. Interleukin-12-activated natural killer cells recognize B7 costimulatory molecules on tumor cells and autologous dendritic cells. Blood 91(1):196-206. [PubMed: 9414285]  [MGI Ref ID J:45067]

Gelman AE; LaRosa DF; Zhang J; Walsh PT; Choi Y; Sunyer JO; Turka LA. 2006. The adaptor molecule MyD88 activates PI-3 kinase signaling in CD4+ T cells and enables CpG oligodeoxynucleotide-mediated costimulation. Immunity 25(5):783-93. [PubMed: 17055754]  [MGI Ref ID J:116106]

Girvin AM; Dal Canto MC; Miller SD. 2002. CD40/CD40L interaction is essential for the induction of EAE in the absence of CD28-mediated co-stimulation. J Autoimmun 18(2):83-94. [PubMed: 11908941]  [MGI Ref ID J:119134]

Girvin AM; Dal Canto MC; Rhee L; Salomon B; Sharpe A; Bluestone JA; Miller SD. 2000. A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: a comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade. J Immunol 164(1):136-43. [PubMed: 10605004]  [MGI Ref ID J:109892]

Graham DB; Bell MP; Huntoon CJ; Griffin MD; Tai X; Singer A; McKean DJ. 2006. CD28 ligation costimulates cell death but not maturation of double-positive thymocytes due to defective ERK MAPK signaling. J Immunol 177(9):6098-107. [PubMed: 17056536]  [MGI Ref ID J:140523]

Gray Parkin K; Stephan RP; Apilado RG; Lill-Elghanian DA; Lee KP; Saha B; Witte PL. 2002. Expression of CD28 by bone marrow stromal cells and its involvement in B lymphopoiesis. J Immunol 169(5):2292-302. [PubMed: 12193694]  [MGI Ref ID J:120690]

Green JM; Karpitskiy V; Kimzey SL; Shaw AS. 2000. Coordinate regulation of T cell activation by CD2 and CD28. J Immunol 164(7):3591-5. [PubMed: 10725714]  [MGI Ref ID J:111620]

Guo F; Iclozan C; Suh WK; Anasetti C; Yu XZ. 2008. CD28 controls differentiation of regulatory T cells from naive CD4 T cells. J Immunol 181(4):2285-91. [PubMed: 18684917]  [MGI Ref ID J:140198]

Habiro K; Kotani M; Omoto K; Kobayashi S; Tanabe K; Shimmura H; Suzuki K; Hayashi T; Toma H; Abe R. 2003. Mechanism of allorecognition and skin graft rejection in CD28 and CD40 ligand double-deficient mice. Transplantation 76(5):854-8. [PubMed: 14501867]  [MGI Ref ID J:126214]

Hagen KA; Moses CT; Drasler EF; Podetz-Pedersen KM; Jameson SC; Khoruts A. 2004. A role for CD28 in lymphopenia-induced proliferation of CD4 T cells. J Immunol 173(6):3909-15. [PubMed: 15356139]  [MGI Ref ID J:92743]

Hancock WW; Tsai TL; Madaio MP; Gasser DL. 2003. Cutting Edge: Multiple autoimmune pathways in kd/kd mice. J Immunol 171(6):2778-81. [PubMed: 12960297]  [MGI Ref ID J:85380]

Hao Z; Duncan GS; Seagal J; Su YW; Hong C; Haight J; Chen NJ; Elia A; Wakeham A; Li WY; Liepa J; Wood GA; Casola S; Rajewsky K; Mak TW. 2008. Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis. Immunity 29(4):615-27. [PubMed: 18835195]  [MGI Ref ID J:141441]

Harada Y; Tokushima M; Matsumoto Y; Ogawa S; Otsuka M; Hayashi K; Weiss BD; June CH; Abe R. 2001. Critical requirement for the membrane-proximal cytosolic tyrosine residue for CD28-mediated costimulation in vivo. J Immunol 166(6):3797-803. [PubMed: 11238622]  [MGI Ref ID J:126654]

Havarinasab S; Haggqvist B; Bjorn E; Pollard KM; Hultman P. 2005. Immunosuppressive and autoimmune effects of thimerosal in mice. Toxicol Appl Pharmacol 204(2):109-21. [PubMed: 15808517]  [MGI Ref ID J:97345]

Hayakawa Y; Takeda K; Yagita H; Van Kaer L; Saiki I; Okumura K. 2001. Differential regulation of Th1 and Th2 functions of NKT cells by CD28 and CD40 costimulatory pathways. J Immunol 166(10):6012-8. [PubMed: 11342617]  [MGI Ref ID J:110892]

Hazlett LD; McClellan S; Barrett R; Rudner X. 2001. B7/CD28 costimulation is critical in susceptibility to Pseudomonas aeruginosa corneal infection: a comparative study using monoclonal antibody blockade and CD28-deficient mice. J Immunol 166(2):1292-9. [PubMed: 11145712]  [MGI Ref ID J:66855]

Heinly C; Sempowski G; Lee D; Patel D; McDermott P; Scearce R; Thompson C; Haynes B. 2001. Comparison of thymocyte development and cytokine production in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient mice. Int Immunol 13(2):157-66. [PubMed: 11157849]  [MGI Ref ID J:67177]

Hendriks J; Xiao Y; Borst J. 2003. CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool. J Exp Med 198(9):1369-80. [PubMed: 14581610]  [MGI Ref ID J:86461]

Herold KC; Lu J; Rulifson I; Vezys V; Taub D; Grusby MJ; Bluestone JA. 1997. Regulation of C-C chemokine production by murine T cells by CD28/B7 costimulation. J Immunol 159(9):4150-3. [PubMed: 9379007]  [MGI Ref ID J:110673]

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Tang Q; Henriksen KJ; Boden EK; Tooley AJ; Ye J; Subudhi SK; Zheng XX; Strom TB; Bluestone JA. 2003. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 171(7):3348-52. [PubMed: 14500627]  [MGI Ref ID J:120383]

Tang Q; Smith JA; Szot GL; Zhou P; Alegre ML; Henriksen KJ; Thompson CB; Bluestone JA. 2003. CD28/B7 regulation of anti-CD3-mediated immunosuppression in vivo. J Immunol 170(3):1510-6. [PubMed: 12538715]  [MGI Ref ID J:126890]

Toto P; Feliciani C; Amerio P; Suzuki H; Wang B; Shivji GM; Woodley D; Sauder DN. 2000. Immune modulation in pemphigus vulgaris: role of CD28 and IL-10. J Immunol 164(1):522-9. [PubMed: 10605050]  [MGI Ref ID J:125983]

Tsukada J; Ozaki A; Hanada T; Chinen T; Abe R; Yoshimura A; Kubo M. 2005. The role of suppressor of cytokine signaling 1 as a negative regulator for aberrant expansion of CD8{alpha}+ dendritic cell subset. Int Immunol 17(9):1167-78. [PubMed: 16091384]  [MGI Ref ID J:100705]

Vacchio MS; Hodes RJ. 2003. CD28 costimulation is required for in vivo induction of peripheral tolerance in CD8 T cells. J Exp Med 197(1):19-26. [PubMed: 12515810]  [MGI Ref ID J:109348]

Vacchio MS; Williams JA; Hodes RJ. 2005. A novel role for CD28 in thymic selection: elimination of CD28/B7 interactions increases positive selection. Eur J Immunol 35(2):418-27. [PubMed: 15657954]  [MGI Ref ID J:95546]

VanLith ML; Kohlgraf KG; Sivinski CL; Tempero RM; Hollingsworth MA. 2002. MUC1-specific anti-tumor responses: molecular requirements for CD4-mediated responses. Int Immunol 14(8):873-82. [PubMed: 12147624]  [MGI Ref ID J:113544]

Vella AT; Mitchell T; Groth B; Linsley PS; Green JM; Thompson CB; Kappler JW; Marrack P. 1997. CD28 engagement and proinflammatory cytokines contribute to T cell expansion and long-term survival in vivo. J Immunol 158(10):4714-20. [PubMed: 9144484]  [MGI Ref ID J:110667]

Vidric M; Suh WK; Dianzani U; Mak TW; Watts TH. 2005. Cooperation between 4-1BB and ICOS in the immune response to influenza virus revealed by studies of CD28/ICOS-deficient mice. J Immunol 175(11):7288-96. [PubMed: 16301634]  [MGI Ref ID J:122143]

Villegas EN; Elloso MM; Reichmann G; Peach R; Hunter CA. 1999. Role of CD28 in the generation of effector and memory responses required for resistance to Toxoplasma gondii. J Immunol 163(6):3344-53. [PubMed: 10477604]  [MGI Ref ID J:119602]

Villegas EN; Lieberman LA; Mason N; Blass SL; Zediak VP; Peach R; Horan T; Yoshinaga S; Hunter CA. 2002. A role for inducible costimulator protein in the CD28- independent mechanism of resistance to Toxoplasma gondii. J Immunol 169(2):937-43. [PubMed: 12097399]  [MGI Ref ID J:123835]

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 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]

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]

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]

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]

Zheng X; Zhang H; Yin L; Wang CR; Liu Y; Zheng P. 2008. Modulation of NKT cell development by B7-CD28 interaction: an expanding horizon for costimulation. PLoS ONE 3(7):e2703. [PubMed: 18628995]  [MGI Ref ID J:139280]

van der Graaf CA; Netea MG; Verschueren I; van der Meer JW; Kullberg BJ. 2005. Differential cytokine production and Toll-like receptor signaling pathways by Candida albicans blastoconidia and hyphae. Infect Immun 73(11):7458-64. [PubMed: 16239547]  [MGI Ref ID J:104193]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.