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 C57BL/10 Donor Strain 129S2 via D3 ES cell line Generation N6F11p Generation Definitions   Donating Investigator Dan Littman,   New York University Medical Center

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Cd4^tm1 targeted mutation have a significant block in CD4⁺ T cell development; 90% of their circulating T cells are CD8⁺. Homozygous mutant mice also show a Class II restricted deficit in helper T cell activity and other T cell responses.

Control Information

	Control
	000665 C57BL/10J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Cd4

010514	B10.Cg-H2g Tg(Cd4-Klra1)6295Dl/J
002663	B6.129S2-Cd4tm1Mak/J
002269	B6.129S6-Cd4tm1Knw/J
002664	B6;129S-Cd4tm1Mak Cd8atm1Mak/J
002268	B6;129S6-Cd4tm1Knw/J
012895	C57BL/6-Tg(Cd4-Il17rb)5Cdon/J
014639	C57BL/6-Tg(Cd4-TcraDN32D3)1Aben/J
014644	C57BL/6-Tg(Cd4-Zbtb16)1797Aben/J
006483	CBy.129S2(B6)-Cd4tm1Mak/J
003090	NOD.129S6(B6)-Cd4tm1Knw/DvsJ
005328	NOD/ShiLt-Tg(Cd4-DsRed)4Lt/J

View Strains carrying other alleles of Cd4     (11 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Cd4^tm1Litt/Cd4^tm1Litt

        involves: 129S2/SvPas

• immune system phenotype
• abnormal CD4-positive T cell physiology
  • antibody production by B cells in response to the T cell dependent antigen TNP-KLH is 10-fold less than in controls   (MGI Ref ID J:50435)
• decreased CD4-positive T cell number
  • mice exhibit a near complete absence of CD4 expression in thymocytes, lamina propria lin-c-kit+CD127+ cells, and splenic TCRbeta-CD19-MHCII+CD11c+ cells compared to in wild-type mice   (MGI Ref ID J:158962)
• • absent CD4-positive T cells
    • CD4 T cells are absent from both the thymus and the periphery   (MGI Ref ID J:50435)
• decreased T cell proliferation
  • CD4 T cells have decreased levels of proliferation in mixed lymphocyte cultures with cells expressing class II alloantigen   (MGI Ref ID J:50435)
• increased CD8-positive T cell number   (MGI Ref ID J:158962)
  • 90% of peripheral alphabeta T cell are CD8-positive   (MGI Ref ID J:50435)
  • 93% of thymocytes are CD8-positive   (MGI Ref ID J:50435)
• hematopoietic system phenotype
• decreased CD4-positive T cell number
  • mice exhibit a near complete absence of CD4 expression in thymocytes, lamina propria lin-c-kit+CD127+ cells, and splenic TCRbeta-CD19-MHCII+CD11c+ cells compared to in wild-type mice   (MGI Ref ID J:158962)
• • absent CD4-positive T cells
    • CD4 T cells are absent from both the thymus and the periphery   (MGI Ref ID J:50435)
• decreased T cell proliferation
  • CD4 T cells have decreased levels of proliferation in mixed lymphocyte cultures with cells expressing class II alloantigen   (MGI Ref ID J:50435)
• increased CD8-positive T cell number   (MGI Ref ID J:158962)
  • 90% of peripheral alphabeta T cell are CD8-positive   (MGI Ref ID J:50435)
  • 93% of thymocytes are CD8-positive   (MGI Ref ID J:50435)
• cellular phenotype
• decreased T cell proliferation
  • CD4 T cells have decreased levels of proliferation in mixed lymphocyte cultures with cells expressing class II alloantigen   (MGI Ref ID J:50435)

View Research Applications

Research Applications

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

Cd4^tm1Litt related

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cd4tm1Litt
Allele Name		targeted mutation, Dan R Littman
Allele Type		Targeted (knock-out)
Common Name(s)		CD4-; Cd4tm1Drl;
Mutation Made By		Dan Littman,   New York University Medical Center
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Cd4, CD4 antigen
Chromosome		6
Gene Common Name(s)		CD4mut; L3T4; Ly-4; W3/25; lymphocyte antigen 4; p55;
Molecular Note		A neomycin resistance gene was inserted into exon 5. No cell surface expression of the encoded protein was detected in T cells and thymocytes derived from homozygous mice (data not shown). [MGI Ref ID J:50435]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Cd4, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Killeen N; Sawada S; Littman DR. 1993. Regulated expression of human CD4 rescues helper T cell development in mice lacking expression of endogenous CD4. EMBO J 12(4):1547-53. [PubMed: 8467804]  [MGI Ref ID J:50435]

Additional References

Cd4^tm1Litt related

Adleman LM; Wofsy D. 1996. Blind T-cell homeostasis in CD4-deficient mice. J Acquir Immune Defic Syndr Hum Retrovirol 11(4):334-40. [PubMed: 8601219]  [MGI Ref ID J:34682]

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]

Barthlott T; Stockinger B. 2001. Lineage fate alteration of thymocytes developing in an MHC environment containing MHC/peptide ligands with antagonist properties. Eur J Immunol 31(12):3595-601. [PubMed: 11745379]  [MGI Ref ID J:151748]

Blache C; Adriouch S; Calbo S; Drouot L; Dulauroy S; Arnoult C; Le Corre S; Six A; Seman M; Boyer O. 2009. Cutting edge: CD4-independent development of functional FoxP3+ regulatory t cells. J Immunol 183(7):4182-6. [PubMed: 19767568]  [MGI Ref ID J:152754]

Blair PJ; Bultman SJ; Haas JC; Rouse BT; Wilkinson JE; Godfrey VL. 1994. CD4+CD8- T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse. J Immunol 153(8):3764-74. [PubMed: 7930593]  [MGI Ref ID J:20865]

Boyer O; Marodon G; Cohen JL; Lejeune L; Irinopoulou T; Liblau R; Bruneval P; Klatzmann D. 2002. Human CD4 expression at the late single-positive stage of thymic development supports T cell maturation and peripheral export in CD4-deficient mice. J Immunol 169(8):4347-53. [PubMed: 12370367]  [MGI Ref ID J:120171]

Bry L; Brenner MB. 2004. Critical role of T cell-dependent serum antibody, but not the gut-associated lymphoid tissue, for surviving acute mucosal infection with Citrobacter rodentium, an attaching and effacing pathogen. J Immunol 172(1):433-41. [PubMed: 14688352]  [MGI Ref ID J:87077]

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]

Burrer R; Buchmeier MJ; Wolfe T; Ting JP; Feuer R; Iglesias A; von Herrath MG. 2007. Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies. Am J Pathol 170(2):557-66. [PubMed: 17255324]  [MGI Ref ID J:117906]

Cao L; Deleo JA. 2008. CNS-infiltrating CD4(+) T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur J Immunol 38(2):448-458. [PubMed: 18196515]  [MGI Ref ID J:131283]

Chan S; Correia-Neves M; Dierich A; Benoist C; Mathis D. 1998. Visualization of CD4/CD8 T cell commitment. J Exp Med 188(12):2321-33. [PubMed: 9858518]  [MGI Ref ID J:113263]

Chesnutt MS; Finck BK; Killeen N; Connolly MK; Goodman H; Wofsy D. 1998. Enhanced lymphoproliferation and diminished autoimmunity in CD4-deficient MRL/lpr mice. Clin Immunol Immunopathol 87(1):23-32. [PubMed: 9576007]  [MGI Ref ID J:47163]

Chong MM; Simpson N; Ciofani M; Chen G; Collins A; Littman DR. 2010. Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells. Genes Dev 24(7):659-69. [PubMed: 20360383]  [MGI Ref ID J:158962]

Collins A; Hewitt SL; Chaumeil J; Sellars M; Micsinai M; Allinne J; Parisi F; Nora EP; Bolland DJ; Corcoran AE; Kluger Y; Bosselut R; Ellmeier W; Chong MM; Littman DR; Skok JA. 2011. RUNX Transcription Factor-Mediated Association of Cd4 and Cd8 Enables Coordinate Gene Regulation. Immunity 34(3):303-14. [PubMed: 21435585]  [MGI Ref ID J:169841]

Davis CB; Killeen N; Crooks ME; Raulet D; Littman DR. 1993. Evidence for a stochastic mechanism in the differentiation of mature subsets of T lymphocytes. Cell 73(2):237-47. [PubMed: 8097431]  [MGI Ref ID J:153274]

Elhage R; Gourdy P; Brouchet L; Jawien J; Fouque MJ; Fievet C; Huc X; Barreira Y; Couloumiers JC; Arnal JF; Bayard F. 2004. Deleting TCR alpha beta+ or CD4+ T lymphocytes leads to opposite effects on site-specific atherosclerosis in female apolipoprotein E-deficient mice. Am J Pathol 165(6):2013-8. [PubMed: 15579444]  [MGI Ref ID J:94976]

Evel-Kabler K; Song XT; Aldrich M; Huang XF; Chen SY. 2006. SOCS1 restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling. J Clin Invest 116(1):90-100. [PubMed: 16357940]  [MGI Ref ID J:105256]

Fujimoto M; Tsutsui H; Xinshou O; Tokumoto M; Watanabe D; Shima Y; Yoshimoto T; Hirakata H; Kawase I; Nakanishi K; Kishimoto T; Naka T. 2004. Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases. Int Immunol 16(2):303-14. [PubMed: 14734616]  [MGI Ref ID J:88972]

Harris DP; Koch S; Mullen LM; Swain SL. 2001. B cell immunodeficiency fails to develop in cd4-deficient mice infected with bm5: murine aids as a multistep disease. J Immunol 166(10):6041-9. [PubMed: 11342621]  [MGI Ref ID J:69348]

He X; Park K; Wang H; He X; Zhang Y; Hua X; Li Y; Kappes DJ. 2008. CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity 28(3):346-58. [PubMed: 18342007]  [MGI Ref ID J:132996]

Ishikawa H; Hisaeda H; Taniguchi M; Nakayama T; Sakai T; Maekawa Y; Nakano Y; Zhang M; Zhang T; Nishitani M; Takashima M; Himeno K. 2000. CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major. Int Immunol 12(9):1267-74. [PubMed: 10967021]  [MGI Ref ID J:110502]

Kawakami K; Kinjo Y; Yara S; Koguchi Y; Uezu K; Nakayama T; Taniguchi M; Saito A. 2001. Activation of Valpha14(+) natural killer T cells by alpha-galactosylceramide results in development of Th1 response and local host resistance in mice infected with Cryptococcus neoformans. Infect Immun 69(1):213-20. [PubMed: 11119508]  [MGI Ref ID J:67758]

Killeen N; Littman DR. 1993. Helper T-cell development in the absence of CD4-p56lck association. Nature 364(6439):729-32. [PubMed: 8355789]  [MGI Ref ID J:113011]

Laub R; Brecht R; Dorsch M; Valey U; Wenk K; Emmrich F. 2002. Anti-Human CD4 Induces Peripheral Tolerance in a Human CD4(+), Murine CD4(-), HLA-DR(+) Advanced Transgenic Mouse Model. J Immunol 169(6):2947-55. [PubMed: 12218108]  [MGI Ref ID J:78960]

Laub R; Dorsch M; Meyer D; Ermann J; Hedrich HJ; Emmrich F. 2000. A multiple transgenic mouse model with a partially humanized activation pathway for helper T cell responses. J Immunol Methods 246(1-2):37-50. [PubMed: 11121545]  [MGI Ref ID J:102719]

Leitenberg D; Boutin Y; Constant S; Bottomly K. 1998. CD4 regulation of TCR signaling and T cell differentiation following stimulation with peptides of different affinities for the TCR. J Immunol 161(3):1194-203. [PubMed: 9686579]  [MGI Ref ID J:118762]

Locksley RM; Reiner SL; Hatam F; Littman DR; Killeen N. 1993. Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice. Science 261(5127):1448-51. [PubMed: 8367726]  [MGI Ref ID J:113010]

Maldonado MA; MacDonald GC; Kakkanaiah VN; Fecho K; Dransfield M; Sekiguchi D; Cohen PL; Eisenberg RA. 1999. Differential control of autoantibodies and lymphoproliferation by Fas ligand expression on CD4+ and CD8+ T cells in vivo. J Immunol 163(6):3138-42. [PubMed: 10477580]  [MGI Ref ID J:119603]

Marschner S; Hunig T; Cambier JC; Finkel TH. 2002. Ligation of human CD4 interferes with antigen-induced activation of primary T cells. Immunol Lett 82(1-2):131-9. [PubMed: 12008044]  [MGI Ref ID J:113525]

Matechak EO; Killeen N; Hedrick SM; Fowlkes BJ. 1996. MHC class II-specific T cells can develop in the CD8 lineage when CD4 is absent. Immunity 4(4):337-47. [PubMed: 8612128]  [MGI Ref ID J:88852]

Miyazaki T; Dierich A; Benoist C; Mathis D. 1996. LAG-3 is not responsible for selecting T helper cells in CD4-deficient mice. Int Immunol 8(5):725-9. [PubMed: 8671660]  [MGI Ref ID J:33272]

Muller KP; Kyewski BA. 1995. Intrathymic T cell receptor (TcR) targeting in mice lacking CD4 or major histocompatibility complex (MHC) class II: rescue of CD4 T cell lineage without co-engagement of TcR/CD4 by MHC class II. Eur J Immunol 25(4):896-902. [PubMed: 7737291]  [MGI Ref ID J:24487]

Rajan TV; Nelson FK; Killeen N; Shultz LD; Yates JA; Bailis JM; Littman DR; Greiner DL. 1994. CD4+ T-lymphocytes are not required for murine resistance to the human filarial parasite, Brugia malayi. Exp Parasitol 78(4):352-60. [PubMed: 7911434]  [MGI Ref ID J:110741]

Santori FR; Arsov I; Lilic M; Vukmanovic S. 2002. Editing autoreactive TCR enables efficient positive selection. J Immunol 169(4):1729-34. [PubMed: 12165493]  [MGI Ref ID J:120705]

Saunders BM; Frank AA; Orme IM; Cooper AM. 2002. CD4 is required for the development of a protective granulomatous response to pulmonary tuberculosis. Cell Immunol 216(1-2):65-72. [PubMed: 12381351]  [MGI Ref ID J:115550]

Serpe CJ; Coers S; Sanders VM; Jones KJ. 2003. CD4+ T, but not CD8+ or B, lymphocytes mediate facial motoneuron survival after facial nerve transection. Brain Behav Immun 17(5):393-402. [PubMed: 12946661]  [MGI Ref ID J:105952]

Steel JC; Ramlogan CA; Yu P; Sakai Y; Forni G; Waldmann TA; Morris JC. 2010. Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help. Cancer Res 70(3):1072-81. [PubMed: 20086176]  [MGI Ref ID J:156863]

Strong J; Wang Q; Killeen N. 2001. Impaired survival of T helper cells in the absence of CD4. Proc Natl Acad Sci U S A 98(5):2566-71. [PubMed: 11226279]  [MGI Ref ID J:67872]

Sun JC; Bevan MJ. 2004. Cutting edge: long-lived CD8 memory and protective immunity in the absence of CD40 expression on CD8 T cells. J Immunol 172(6):3385-9. [PubMed: 15004136]  [MGI Ref ID J:88609]

Tatari-Calderone Z; Brogdon JL; Tinsley KW; Ramezani A; Leitenberg D. 2005. CD4-dependent signaling is required for a late checkpoint during Th2 development associated with resistance to activation-induced cell death. J Immunol 175(9):5629-36. [PubMed: 16237052]  [MGI Ref ID J:119360]

Tinsley KW; Herzog D; Leitenberg D. 2011. CD4 co-receptor dependent signaling promotes competency for re-stimulation induced cell death of effector T cells. Cell Immunol 266(2):200-7. [PubMed: 21071017]  [MGI Ref ID J:167010]

Wang Q; Strong J; Killeen N. 2001. Homeostatic competition among T cells revealed by conditional inactivation of the mouse Cd4 gene. J Exp Med 194(12):1721-30. [PubMed: 11748274]  [MGI Ref ID J:73479]

Zhou X; Robertson AK; Rudling M; Parini P; Hansson GK. 2005. Lesion development and response to immunization reveal a complex role for CD4 in atherosclerosis. Circ Res 96(4):427-34. [PubMed: 15662027]  [MGI Ref ID J:106869]

von Herrath MG; Yokoyama M; Dockter J; Oldstone MB; Whitton JL. 1996. CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge. J Virol 70(2):1072-9. [PubMed: 8551565]  [MGI Ref ID J:30536]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• 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
	000665 C57BL/10J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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