Murine Models of Immunodeficiency and Autoimmune Disease

Philip Cohen1

1 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Publication Name:  Current Protocols in Immunology
Unit Number:  Appendix 1E
DOI:  10.1002/0471142735.ima01es17
Online Posting Date:  May, 2001
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


Genetically determined murine immunodeficiency states are useful for understanding the function of specific immune‐system genes and cellpopulations. In addition, certain immunodeficient strains may be exploited as hosts for foreign tumors or immune cells. The more commonly used immunodeficiency models are described in this appendix. Not included are strains better known for primary neurological or neuromuscular abnormalities or for defective osteoclast function. Many of the recently described immune‐deficient “knockout” strains are described, including cytokine and cytokine receptor knockout strains. The most widely studied murine strains for autoimmune disease and experimental autoreactivity are also listed.

PDF or HTML at Wiley Online Library

Table of Contents

  • Literature Cited
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Alberola‐Ila, J., Forbush, K.A., Seger, R., Krebs, E.G., and Perlmutter, R.M. 1995. Selective requirement for MAP kinase activation in thymocyte differentiation. Nature 373:620‐623.
   Andrews, B.S., Eisenberg, R.A., Theofilopoulos, A.N., Izui, S., Wilson, C.B., McConahey, P.J., Murphy, E.D., Roths, J.B., and Dixon, F.J. 1978. Spontaneous murine lupus‐like syndromes. Clinical and immunopathological manifestations in several strains. J. Exp. Med. 148:1198‐1215.
   Arbones, M.L., Ord, D.C., Ley, K., Ratech, H., Maynard‐Curry, C., Otten, G., Capon, D.J., and Tedder, T.F. 1994. Lymphocyte homing and leukocyte rolling and migration are impaired in L‐selectin‐deficient mice. Immunity 1:247‐260.
   Bikoff, E.K., Huang, L.Y., Episkopou, V., van Meerwijk, J., Germain, R.N., and Robertson, E.J. 1993. Defective major histocompatibiity complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression. J. Exp. Med. 177:1699‐1712.
   Bonneville, M., Ishida, I., Itohara, S., Verbeek, S., Berns, A., Kanagawa, O., Haas, W., and Tonegawa, S. 1990. Self‐tolerance to transgenic gamma‐delta T cells by intrathymic inactivation. Nature 344:163‐165.
   Bosma, G.C., Custer, R.C., and Bosma, M.J. 1983. A severe combined immunodeficiency mutation in the mouse. Nature 301:527‐530.
   Bosma, G.C., Fried, M.R., Custer, R.P., Carroll, A., Gibson, D.M., and Bosma, M.J. 1988. Evidence of functional lymphocytes in some (leaky) scid mice. J. Exp. Med. 167:1016‐1033.
   Bosma, G.C., Davisson, M.T., Reutsch, N.R., Sweet, H.O., Shultz, L.D., and Bosma, M.J. 1989. The mouse mutation severe combined immune deficiency (scid) is on chromosome 16. Immunogenetics 29:54‐57.
   Buckwalter, M.S., Katz, R.W., and Camper, S.A. 1991. Localization of the panhypopituitary dwarf mutation (df) on mouse chromosome 11 in an intersubspecific backcross. Genomics 10:515‐526.
   Burkly, L., Hession, C., Ogata, L., Reilly, C., Marconi, L.A., Olson, D., Tizard, T., Cate, R., and Lo, D. 1995. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 373:531‐536.
   Cacalano, G., Lee, J., Kikly, K., Ryan, A.M., Pitts‐Meek, S., Hultgren, B., Wood, W.I., and Moore, M.W. 1994. Neutrophil and B cell expansion in mice that lack the murine IL‐8 receptor homolog. Science 265:682‐684.
   Cachon‐Gonzalez, M.B., Fenner, S., Coffin, J.M., Moran, C., Best, S., and Stoye, J.P. 1994. Structure and expression of the hairless gene of mice. Proc. Natl. Acad. Sci. U.S.A. 91:7717‐7721.
   Castigli, E., Alt, F.W., Davidson, L., Bottaro, A., Mizoguchi, E., Bhan, A.K., and Geha, R.S. 1994. CD40‐deficient mice generated by recombination‐activating gene‐2‐deficient blastocyst complementation. Proc. Natl. Acad. Sci. U.S.A. 91:12135‐12139.
   Chen, J., Trounstine, M., Kurahara, C., Young, F., Kuo, C.C., Xu, Y., Loring, J.F., Alt, F.W., and Huszar, D. 1993. B cell development in mice that lack one or both immunoglobulin kappa light chain genes. EMBO J. 12:821‐830.
   Clark, E.A., Shultz, L.D., and Pollak, S.B. 1981. Mutations in mice that influence natural killer (NK) activity. Immunogenetics 12:601‐613.
   Cohen, D.I., Hedrick, S.M., Nielsen, E.A., D'Eustachio, P., Ruddle, F., Steinberg, A.D., Paul, W.E., and Davis, M.M. 1985a. Isolation of a cDNA clone corresponding to an X‐linked gene family (XLR) closely linked to the murine immunodeficiency disorder xid. Nature 314:369‐372.
   Cohen, D.I., Steinberg, A.D., Paul, W.E., and Davis, M.M. 1985b. Expression of an X‐linked gene family (XLR) in late‐stage B cells and its alteration by the xid mutation. Nature 314:372‐374.
   Cohen, P.L. and Eisenberg, R.A. 1991. Lpr and gld: Single gene models of systemic autoimmunity and lymphoproliferative disease. Annu. Rev. Immunol. 9:243‐269.
   Cook, D.N., Beck, M.A., Coffman, T.M., Kirby, S.L., Sheridan, J.F., Pragnell, I.B., and Smithies, O. 1995. Requirement of MIP‐1α for an inflammatory response to viral infection. Science 269:1583‐1585.
   Corcoran, L.M., Karvelas, M., Nossai, G.J., Ye, Z.S., Jacks, T., and Baltimore, D. 1993. Oct‐2, although not required for early B cell development, is critical for later B cell maturation and for postnatal survival. Genes & Dev. 7:570‐581.
   Cosgrove, D., Gray, D., Dierich, A., Kaufman, J., Lemeur, M., Benoist, C., and Mathis, D. 1991. Mice lacking MHC class II molecules. Cell 66:1051‐1066.
   Dalton, D.K., Pitts‐Meek, S., Keshav, S., Figari, I.S., Bradley, A., and Stewart, T. 1993. Multiple defects of immune cell function in mice with disrupted interferon γ genes. Science 259:1739‐1742.
   Datta, S.K. 1988. Murine lupus. Methods Enzymol. 162:385‐412.
   Datta, S.K. 1989. A search for the underlying mechanisms of systemic autoimmune disease in the NZB × SWR model. Clin. Immunol. Immunopathol. 51:141‐156.
   Davidson, W.F. 1982. Immunologic abnormalities of the autoimmune mouse, Palmerston North. J. Immunol. 129:751‐758.
   Davidson, W.F., Morse, H.C. III, Sharrow, S.O., and Chused, T.M. 1979. Phenotypic and functional effects of the motheaten gene on murine B and T lymphocytes. J. Immunol. 122:884‐891.
   DeTogni, P., Goellner, J., Ruddle, N.H., Streeter, P.R., Fick, A., Mariathasan, S., Smith, S.C., Carlson, R., Shornick, L.P., and Strauss‐Schoenberger, J. 1994. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 263:703‐707.
   Dent, A.L., Matis, L.A., Hooshmand, F., Widacki, S.M., Bluestone, J.A., and Hedrick, S.M. 1990. Self‐reactive gamma‐delta T cells are eliminated in the thymus. Nature 343:714‐719.
   DiSanto, J.P., Muller, W., Guy‐Grand, D., Fischer, A., and Rajewsky, K. 1995. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor γ chain. Proc. Natl. Acad. Sci. U.S.A. 92:377‐381.
   Dombrowicz, D., Flamand, V., Brigman, K.K., Koller, B.H., and Kinet, J.P. 1993. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor α chain gene. Cell 75:969‐976.
   Domen, J., van der Lugt, N.M., Acton, D., Laird, P.W., Linders, K., and Berns, A. 1993. Pim‐1 levels determine the size of early B lymphoid compartments in bone marrow. J. Exp. Med. 178:1665‐1673.
   Dranoff, G., Crawford, A.D., Sadelain, M., Ream, B., Rashid, A., Bronson, R.T., Dickersen, G.R., Bachurski, C.J., Whitsett, J.A., and Mulligan, R.C. 1994. Involvement of granulocyte‐macrophage colony‐stimulating factor in pulmonary homeostasis. Science 264:713‐716.
   Dumont, F., Robert, F., and Bischoff, P. 1979. T and B lymphocytes in pituitary dwarf Snell‐Bagg mice. Immunology 38:25‐31.
   Duquesnoy, R.J., Christensen, K., Pederson, G.M., and Kemp, R.G. 1975. Development of immunodeficiency of pituitary dwarf mice. Am. Zool. 15:167‐174.
   Eisenberg, R.A., Izui, S., McConahey, P.J., Hang, L., Peters, C.J., Theofilopoulos, A.N., and Dixon, F.J. 1980. Male determined accelerated autoimmune disease in BXSB mice: Transfer by bone marrow and spleen cells. J. Immunol. 125:1032‐1036.
   Engel, P., Zhou, L., Ord, D.C., Sato, S., Koller, B., and Tedder, T.F. 1995. Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 3:39‐50.
   Erickson, S.L., de Sauvage, P.J., Kikly, K., Carver‐Moore, M.W., Pitts‐Meek, S., Sheehan, K.C., Schreiber, R.D., Coeddel, D.V., and Moore, M.W. 1994. Decreased sensitivity to tumour‐necrosis factor but normal T‐cell development in TNF receptor‐2‐deficient mice. Nature 372:560‐563.
   Erikson, J., Radic, M.Z., Camper, S.A., Hardy, R.R., Carmack, C., and Weigert, M. 1991. Expression of anti‐DNA immunoglobulin transgenes in non‐autoimmune mice. Nature 349:331‐334.
   Escary, J.L., Perreau, J., Dumenil, D., Ezine, S., and Brulet, P. 1993. Leukemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation. Nature 363:361‐364.
   Ezoe, K., Holmes, S.A., Ho, L., Bennett, C.P., Bolognia, J.L., Brueton, L., Burn, J., Fallabella, R., Gatto, E.M., Ishii, N., Moss, C., Pittelkow, M.R., Thompson, E., Ward, K.A., and Spritz, R.A. 1995. Novel mutations and deletions of the kit (steel factor receptor) gene in human piebaldism. Am. J. Hum. Genet. 56:58‐66.
   Fattori, E., Cappelletti, M., Costa, P., Sellitto, C., Cantoni, L., Carelli, M., Faggioni, R., Fantuzzi, G., Ghezzi, P., and Poli, V. 1994. Defective inflammatory response in interleukin‐6‐deficient mice. J. Exp. Med. 180:1243‐1250.
   Fehling, H.J., Swat, W., Laplace, C., Kühn, R., Rajewsky, K., Muller, U., and von Boehmer, H. 1994. MHC class I expression in mice lacking the proteosome subunit LMP‐7. Science 265:1234‐1237.
   Fehling, H.J., Krotkova, A., Saint‐Ruf, C., and von Boehmer, H. 1995. Crucial role of the pre‐T‐cell receptor α gene in development of α/β but not γ/δ T cells. Nature 375:795‐798.
   Ferrick, D.A. 1994. Transgenic Mice as an in Vivo Model for Self Reactivity, R.G. Landes Co. Austin, Tex.
   Fischer, K.‐D., Zmuldzinas, A., Gardner, S., Barbacid, M., Bernstein, A., and Guidos, C. 1995. Defective T‐cell receptor signalling and positive selection of Vav‐deficient CD4+CD8+ thymocytes. Nature 374:474‐477.
   Fletcher, M.P., Ikeda, R.M., and Gershwin, M.E. 1977. Splenic influence of T cell function. The immunobiology of the inbred hereditarily asplenic mouse. J. Immunol. 119:110‐117.
   Freeman, G.J., Borriello, F., Hodes, R.J., Reiser, H., Hathcock, K.S., Laszlo, G., McKnight, A.J., Kim, J., Du, L., and Lombard, D.B. 1993. Uncovering of functional alternative CTLA‐4 counter‐receptor in B7‐deficient mice. Science 262:907‐909.
   Fung‐Leung, W.P., Kündig, T.M., Zinkernagel, R.M., and Mak, T.W. 1991a. Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression. J. Exp. Med. 174:1425‐1429.
   Fung‐Leung, W.P., Schilham, M.W., Ramentulla, A., Kündig, T.M., Vollenweider, M., Potter, J., van Ewijk, W., and Mak, T.W. 1991b. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell 65:443‐449.
   Gasser, D.L. and Fischgrund, T. 1973. Genetic control of the immune response in mice. IV. Relationship between graft vs. host reactivity and possession of the high tumor genotypes Ay/a and Avy/a. J. Immunol. 110:305‐308.
   Georgopoulos, K., Bigby, M., Wang, J.H., Molnar, A., Wu, P., Winandy, S., and Sharpe, A. 1994. The Ikaros gene is required for the development of all cell lineages. Cell 79:143‐156.
   Gilfillan, S., Dierich, A., Lemeur, M., Benoist, C., and Mathis, D. 1993. Mice lacking TdT: Mature animals with an immature lymphocyte repertoire. Science 261:1175‐1178.
   Gleichmann, E., Van Elven, E.H., and Van der Veen, J.P.W. 1982. A systemic lupus erythematosus (SLE)‐like disease in mice induced by abnormal T‐B cooperation. Preferential formation of autoantibodies characteristic of SLE. Eur. J. Immunol. 12:152‐159.
   Goodnow, C.C., Crosbie, J., Adelstein, S., Lavoie, T.B., Smith‐Gill, S.J., Brink, R.A., Pritchard‐Briscoe, H., Wotherspoon, J.S., Loblay, R.H., Raphael, K., Trent, R.J., and Basten, A. 1988. Altered immunoglobulin expression and functional silencing of self‐reactive B lymphocytes in transgenic mice. Nature 334:676‐682.
   Green, M.C. and Shultz, L.D. 1975. Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology. J. Hered. 66:250‐258.
   Grusby, M.J., Johnson, R.S., Papaioannou, V.E., and Glimcher, L.H. 1991. Depletion of CD4+ T cells in major histocompatibility complex class II–deficient mice. Science 253:1417‐1420.
   Hanafusa, T. and Tarui, S. 1990. Immune pathogenesis of diabetes in the nonobese diabetic mouse: An overview. Curr. Top. Microbiol. Immunol. 156:15‐25.
   Heusel, J.W., Wesselschmidt, R.L., Shresta, S., Russell, J.R., and Ley, T.J. 1994. Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells. Cell 76:977‐987.
   Higgins, M., Hill, R.E., and West, J.D. 1992. Dominant hemimelia and En‐1 on mouse chromosome 2 are not allelic. Genet. Res. 60:53‐60.
   Holub, M. 1989. Immunology of Nude Mice. CRC Press, Boca Raton, Fla.
   Huang, S., Hendriks, W., Althage, A., Hemm, S., Bluethmann, H., Kemijo, R., Vilcek, J., Zinkernagel, R., and Aguet, M. 1993. Immune response in mice that lack the interferon γ receptor. Science 259:1742‐1745.
   Huang, E., Nocka, K., Beier, D.R., Chu, T.Y., Buck, J., Lahm, H.W., Wellner, D., Leder, P., and Besmer, P. 1990. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c‐kit receptor, the gene product of the W locus. Cell 63:225‐233.
   Iwakura, Y., Tosu, M., Yoshida, E., Takiguchi, M., Sato, K., Kitajima, I., Nishioka, K., Yamamoto, K., Takeda, T., Hatanaka, M., Yamamoto, H., and Sekiguchi, T. 1991. Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV‐1. Science 253:1026‐1028.
   Jackson, S.H., Gallin, J.I., and Holland, S.M. 1995. The p47phox mouse knock‐out model of chronic granulomatous disease. J. Exp. Med. 182:751‐758.
   Jacob, C. 1994. Overexpression and Knockout of Cytokines in Transgenic Mice, Harcourt Brace & Co., New York.
   Jung, S., Rajewsky, K., and Radbruch, A. 1993. Shutdown of class switch recombination by deletion of a switch region control elelment. Science 259:984‐987.
   Kagi, D., Ledermann, B., Bürki, K., Seiler, P., Odermatt, B., Olsen, K.J., Podack, E.R., Zinkernagel, R.M., and Hengartner, H. 1994. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin‐deficient mice. Nature 369:31‐37.
   Kawabe, T., Naka, T., Yoshida, K., Tanaka, T., Fujiwara, H., Suematsu, S., Yoshida, N., Kishimoto, T., and Kikutani, H. 1994. The immune responses in CD40‐deficient mice: Impaired immunoglobulin class switching and germinal center formation. Immunity 1:167‐178.
   Kawaji, H., Tsukuda, R., and Nakaguchi, T. 1980. Immunopathology of rhino mouse, an autosomal recessive mutant with murine lupus‐like disease. Acta Pathol. Jpn. 30:515‐530.
   Killeen, N., Stuart, S.G., and Littman, D.R. 1992. Development and function of T cells in mice with a disrupted CD2 gene. EMBO J. 11:4329‐4336.
   Kirchgessner, C.U., Patil, C.K., Evans, J.W., Cuomo, C.A., Fried, L.M., Carter, T., Oettinger, M.A., and Brown, J.M. 1995. DNA‐dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267:1178‐1183.
   Kishihara, K., Penninger, J., Wallace, V.A., Kündig, T.M., Kawai, K., Wakeham, A., Timms, E., Pfeffer, K., Ohashi, P.S., and Thomas, M.L. 1994. Lymphocyte populations and immune responses in CD5‐deficient mice. Eur. J. Immunol. 24:1678‐1684.
   Kitamura, D., Roes, J., Kühn, R., and Rajewsky, K. 1991. A B‐cell‐deficient mouse by targeted disruption of the membrane exon of the immunoglobulin µ chain gene. Nature 350:423‐426.
   Kitamura, D., Kudo, A., Schaal, S., Muller, W., Melchers, F., and Rajewsky, K. 1992. A critical role of Lambda 5 protein in B cell development. Cell 69:823‐831.
   Kitamura, Y. and Go, S. 1979. Decreased production of mast cells in Sl/Sld anemic mice. Blood 53:492‐497.
   Koller, B.H., Marrack, P., Kappler, J.W., and Smithies, O. 1990. Normal development of mice deficient in beta‐2M, MHC class I proteins, and CD8+ T cells. Science 248:1227‐1230.
   Komori, T., Okada, A., Stewart, V., and Alt, F.W. 1993. Lack of H regions in antigen receptor variable region genes of TdT‐deficient lymphocytes. Science 261:1171‐1175.
   Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R.M., Bluethmann, H., and Kohler, G. 1994. Impaired immune and acute‐phase responses in interleukin‐6‐deficient mice. Nature 368:339‐342.
   Koyasu, S., Hussey, R.E., Clayton, L.K., Lerner, A., Pederson, R., Delany‐Heiken, P., Chau, F., and Reinherz, E.L. 1994. Targeted disruption within the CD3 ζ/η/θ/Oct‐ 1 locus in mouse. EMBO J. 13:784‐797.
   Kühn, R., Rajewsky, K., and Muller, W. 1991. Generation and analysis of interleukin‐4‐deficient mice. Science 254:707‐710.
   Kühn, R., Lohler, J., Rennick, D., Rajewsky, K., and Muller, W. 1993. Interleukin‐10‐deficient mice develop chronic enterocolitis. Cell 75:263‐274.
   Kuida, K., Lippke, J.A., Ku, G., Harding, M.W., Livingston, D.J., Su, M.S., and Flavell, R.A. 1995. Altered cytokine export and apoptosis in mice deficient in interleukin‐1β‐converting enzyme. Science 267:2000‐2003.
   Kulkarni, A.B., Huli, C.G., Becker, D., Geiser, A., Lyght, M., Flanders, K.G., Roberts, A., Sporn, M.B., Ward, J.M., and Karlsson, S. 1993. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. U.S.A. 90:770‐774.
   Kündig, T.M., Schorle, H., Bachmann, M.F., Hengartner, H., Zinkernagel, R.M., and Horak, I. 1993. Immune responses in interleukin‐2‐deficient mice. Science 262:1059‐1061.
   Laird, P.W., van der Lugt, N.M., Clarke, A., Domen, J., Linders, K., McWhir, J., Berns, A., and Hopper, M. 1993. In vivo analysis of Pim‐1 deficiency. Nucl. Acids. Res. 21:4750‐4755.
   Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C., McDowell, J., Paskind, M., Rodman, L., and Salfeld, J. 1995. Mice deficient in IL‐1β‐converting enzyme are defective in production of mature IL‐1β and resistant to endotoxic shock. Cell 80:401‐411.
   Lin, H. and Grosschedl, R. 1995. Failure of B cell differentiation in mice lacking the transcription factor EBF. Nature 376:263‐267.
   Lin, C., Lin, S.C., Chang, C.P., and Rosenfield, M.G. 1992. Pit‐1‐dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth. Nature 360:765‐768.
   Lowell, C.A., Soriano, P., and Varmus, H.E. 1994. Functional overlap in the src gene family: Inactivation of hck and fgr impairs natural immunity. Genes & Dev. 8:387‐398.
   Mahoney, K.H., Morse, S.S., and Morahan, P.S. 1980. Macrophage functions in beige (Chediak‐Higashi syndrome) mice. Cancer Res. 40:3934‐3939.
   Malissen, M., Gillet, A., Rocha, B., Trucy, J., Vivier, E., Boyer, C., Kontgen, F., Brun, N., Mazza, G., and Spanopoulou, E. 1993. T cell development in mice lacking the CD3‐ ζ/η gene. EMBO J. 12:4347‐4355.
   Manjumath, N., Correa, M., Ardman, M., and Ardman, B. 1995. Negative regulation of T‐cell adhesion and activation by CD43. Nature 377:535‐537.
   Matsuzawa, A., Moriyama, T., Kaneko, T., Tanaka, M., Kimura, M., Ikeda, H., and Katagiri, T. 1990. A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse. J. Exp. Med. 171:519‐531.
   Mayadas, T.N., Johnson, R.C., Rayburn, H., Hynes, R.O., and Wagner, D.D. 1993. Leukocyte rolling and extravasation are severely compromised in P‐selectin‐deficient mice. Cell 74:541‐554.
   McCune, J.M., Namikawa, R., Kaneshima, H., Shultz, L.D., Lieberman, M., and Weissman, I.L. 1988. The SCID‐hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function. Science 241:1632‐1639.
   Miller, B.J., Appel, M.C., O'Neil, J.J., and Wicker, L.S. 1988. Both the Lyt‐2+ and L3T4+ T cell subsets are required for the transfer of diabetes in nonobese diabetic mice. J. Immunol. 140:52‐58.
   Miyawaki, S., Nakamura, Y., Suzuka, H., Koba, M., Yasumizu, R., Ikehara, S., and Shibata, Y. 1994. A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice. Eur. J. Immunol. 24:429‐434.
   Molina, T.J., Kishihara, K., Siderovski, D.P., van Ewijk, W., Naendran, A., Timms, E., Wakehan, A., Paige, C.J., Hartmann, K.U., and Veillette, A. 1993. Profound block in thymocyte development in mice lacking p56lck. Nature 357:161‐164.
   Möller, G. 1991. Transgenic mice and immunological tolerance. Immunol. Rev. 122:5‐204.
   Mombaerts, P., Iacomin, J., Johnson, R.S., Herrup, K., Tonaguare, S., and Papiacannou, V.E. 1992. RAG‐1‐deficient mice have no B and T lymphocytes. Cell 68:869‐877.
   Mombaerts, P., Mizoguchi, E., Grusby, M.J., Glimcher, L.H., Bhan, A.K., and Tonegawa, S. 1993. Spontaneous development of inflammatory bowel disease in T cell receptor mutants. Cell 75:203‐205.
   Monier, J.C. and Sepetjian. 1975. Spontaneous antinuclear autoimmunisation in swan and nude mice: Comparative study. Ann. Immunol. (Inst. Pasteur) 126C:63‐75.
   Morris, S.C., Cohen, P.L., and Eisenberg, R.A. 1990. Experimental induction of systemic lupus erythematosus by recognition of foreign Ia. Clin. Immunol. Immunopathol. 57:263‐273.
   Morrisey, P.J., Parkinson, D.R., Schwartz, R.S., and Waksal, S.D. 1980. Immunologic abnormalities in HRS/J mice. I. Specific defect in T lymphocyte helper T cell function in a mutant mouse. J. Immunol. 125:1558‐1562.
   Motoyama, N., Wang, F., Roth, K.A., Sawa, H., Nakayama, K.‐I., Nakayama, K., Negishi, I., Senju, S., Zhang, Q., Fujii, S., and Loh, D.Y. 1995. Massive cell death of immature hematopoietic cells and neurons in Bcl‐x‐deficient mice. Science 267:1506‐1510.
   Muller, C., Steinoff, U., Reis, L.P., Hemmi, S., Pavlovic, J., Zinkernagel, R., and Aguet, N. 1994. Functional role of type I and type II interferons in antiviral disease. Science 264:1918‐1921.
   Murakami, M., Tsubata, T., Okamoto, M., Shimizu, A., Kumagai, S., Imura, H., and Honjo, T. 1992. Antigen‐induced apoptotic death of Ly‐1 B cells responsible for autoimmune disease in transgenic mice. Nature 357:14‐15.
   Nakayama, K., Nakayama, K.‐I., Negishi, I., Kuida, K., Sawa, H., and Loh, D.Y. 1994. Targeted disruption of Bcl‐2α‐β in mice: Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. Proc. Natl. Acad. Sci. U.S.A. 91:3700‐3704.
   Nakayama, K.‐I., Nakayama, K., Negishi, I., Kuida, K., Shinkai, Y., Louie, M.C., Fields, L.E., Lucas, P.J., Stewart, V., Alt, F.W., and Loh, D.Y. 1993. Disappearance of the lymphoid system in Bcl‐2 homozygous mutant chimeric mice. Science 261:1584‐1588.
   Negishi, I., Motoyama, N., Nakayama, K.‐I., Nakayama, K., Senju, S., Hatakeyama, S., Zhang, Q., Chan, A.C., and Loh, D.Y. 1995. Essential role for ZAP‐70 in both positive and negative selection of thymocytes. Nature 376:435‐438.
   Nehis, M., Pfeifer, D., Schorpp, M., Hedrich, H., and Boehm, T. 1994. New member of the winged‐helix protein family disrupted in mouse and rat nude mutations. Nature 372:103‐107.
   Nemazee, D. and Bürki, K. 1989. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti–MHC class I antibody genes. Nature 337:562‐566.
   Nitschke, L., Kosco, W.H., Kohler, G., and Lamers, M.C. 1993. Immunoglobulin D–deficient mice can mount normal immune responses to thymus‐independent and ‐dependent antigens. Proc. Natl. Acad. Sci. U.S.A. 90:1887‐1891.
   Oettgen, H.C., Martin, T.S., Synshaw, B.A., Deng, C., Drazen, J.M., and Leder, P. 1994. Active anaphylaxis in IgE‐deficient mice. Nature 370:367‐370.
   Okamoto, M., Murakami, M., Shimizu, A., Ozaki, S., Tsubata, T., Kumagai, S., and Honjo, T. 1992. A transgenic model of autoimmune hemolytic anemia. J. Exp. Med. 175:71‐79.
   Peschon, J.J., Morrissey, P.J., Grabstein, K.E., Ramsdell, F.J., Marakovsky, E., Gilniak, B.C., Park, L.S., Ziegler, S.P., Williams, D.E., and Ware, C.B. 1994. Early lymphocyte expansion is severely impaired in interleukin 7 receptor–deficient mice. J. Exp. Med. 180:1955‐1960.
   Pfeffer, K., Matsuyama, T., Kündig, T.M., Wakeham, A., Kisnihara, K., Shahinian, A., Wiegmann, K., Ohashi, P.S., Kronkle, M., and Mak, T.W. 1993. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73:453‐467.
   Rahemtulla, A., Fung‐Leung, W.P., Schilham, M.W., Kündig, T.M., Sambhara, S.R., Narendran, A., Arabian, A., Wakeham, A., Paige, C.J., Zinkernagel, R.M., Miller, R.G., and Mak, T.W. 1991. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature 353:180‐184.
   Rawlings, D.J., Saffran, D.C., Tsukada, S., Largaespada, D.A., Grimaldi, J.C., Cohen, L., Mohr, R.N., Bazan, J.F., Howard, M., Copeland, N.G., Jankins, N.A., and Witte, O.N. 1993. Mutation of a unique region of Bruton's tyrosine kinase in immunodeficient xid mice. Science 261:358‐361.
   Renshaw, B.R. III, Fanslow, W.C., Armitage, R.J., Campbell, K.A., Liggitt, D., Wright, B., Davison, B.L., and Maliszweksi, C.R. 1994. Humoral immune responses in CD40 ligand–deficient mice. J. Exp. Med. 180:1889‐1900.
   Rickert, R.C., Rajewsky, K., and Roes, J. 1995. Impairment of T‐cell‐dependent B‐cell responses and B‐1 cell development in CD19‐deficient mice. Nature 376:352‐355.
   Roberts, D.W., Wolff, G.L., and Campbell, W.L. 1984. Differential effects of the mottled yellow and pseudoagouti phenotypes in immunocompetence in Avy/a mice. Proc. Natl. Acad. Sci. U.S.A. 81:2152‐2156.
   Rosenstreich, D.L. and Glode, L.M. 1975. Differences in B cell mitogen responsiveness between closely related strains of mice. J. Immunol. 115:777‐781.
   Sadlack, B., Merz, H., Schorle, H., Schimpl, A., Feller, A.C., and Horak, I. 1993. Ulcerative colitis‐like disease in mice with a disrupted interleukin‐2 gene. Cell 75:203‐205.
   Scher, I. 1982. The CBA/N mouse strain: An experimental model illustrating the influence of the X‐chromosome on immunity. Adv. Immunol. 33:1‐71.
   Schwartzenberg, P.L., Stall, A.M., Hardin, J.D., Bowdish, K.S., Hamaran, T., Boast, S., Harbison, M.L., Robertson, E.J., and Goff, S.P. 1991. Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations. Cell 65:1165‐1175.
   Searle, A.G. 1959. Hereditary absence of spleen in the mouse. Nature 184:1419‐1420.
   Shalaby, F., Rossant, J., Yamaguchi, T.P., Gertsenstein, M., Wu, X.‐F., Breitman, M.L., and Schuh, A.C. 1995. Failure of blood‐island formation and vasculogenesis in Flk‐1‐deficient mice. Nature 376:62‐66.
   Shilham, M.W., Fung‐Leung, W.P., Rahemtulla, A., Kuendig, T., Zhang, L., Potter, J., Miller, R.G., Hengartner, H., and Mak, T.W. 1993. Alloreactive cytotoxic T cells can develop and function in mice lacking both CD4 and CD8. Eur. J. Immunol. 23:1299‐1304.
   Shinkai, Y., Rathbun, G., Lam, K.P., Oltz, E.M., Stewart, V., Mendelsohn, M., Charron, J., Datta, M., Young, F., and Stall, A.M. 1992. RAG‐2‐deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68:855‐867.
   Shivdasani, R., Mayer, E.L., and Orkin, S.H. 1995. Absence of blood formation in mice lacking the T‐cell leukaemia oncoprotein tal‐1/SCL. Nature 373:432‐434.
   Shultz, L.D. and Sidman, C.L. 1987. Genetically determined murine models of immunodeficiency. Annu. Rev. Immunol. 5:367‐403.
   Shultz, L.D., Schweitzer, P.A., Rajan, T.V., Yi, T., Ihle, J.N., Matthews, R.J., Thomas, M.L., and Beier, D.R. 1993. Mutations at the murine motheaten locus are within the hematopoietic cell protein‐tyrosine phosphate (Hcph) gene. Cell 73:1445‐1454.
   Sligh, J.E. Jr., Ballantyne, C.M., Rich, S.S., Hawkins, H.K., Smith, C.W., Bradley, A., and Beaudet, A.L. 1993. Inflammatory and immune responses are impaired in mice deficient in the intercellular adhesion molecule 1. Proc. Natl. Acad. Sci. U.S.A. 90:8529‐8533.
   Stanley, E., Lieschke, G.J., Grail, D., Metcalf, D., Hodgson, G., Gail, J.A., Maher, D.W., Cebon, J., Sinickas, V., and Dunn, A.R. 1994. Granulocyte/macrophage colony‐stimulating factor–deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc. Natl. Acad. Sci. U.S.A. 91:5592‐5596.
   Stein, P.L., Lee, H.M., Rich, S., and Soriano, P. 1992. pp59fyn mutant mice display differential signaling in thymocytes and peripheral T cells. Cell 70:741‐750.
   Stief, A., Texido, G., Sansig, G., Eibel, H., LeGros, G., and van der Putten, H. 1994. Mice deficient in CD23 reveal its modulatory role in IgE production but no role in T and B cell development. J. Immunol. 152:3378‐3390.
   Takahashi, T., Tanaka, M., Brannan, C.I., Copeland, N.G., Suda, T., and Nagata, S. 1994. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76:969‐976.
   Takai, M., Li, M., Sylvestre, D., Clynes, R., and Ravetch, J.V. 1994. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell 76:519‐529.
   Takaoki, M. and Kawaji, H. 1980. Impaired antibody response against T‐dependent antigens in rhino mice. Immunology 40:27‐32.
   Takeda, S., Zou, Y.R., Bluethmann, H., Kitamura, D., Muller, U., and Rajewsky, K. 1993. Deletion of the immunoglobulin kappa chain intron enhancer abolishes kappa chain gene rearrangement in cis but not lambda chain gene rearrangement in trans. Proc. Natl. Acad. Sci. U.S.A. 90:2329‐2336.
   Tanaka, S., Suzuki, T., Sakaizumi, M., Harada, Y., Matsushima, Y., Miyashita, M., Fukumori, Y., Inai, S., Moriwaki, K., and Yanekawa, H. 1991. Gene responsible for deficient activity of the beta subunit of C8, the eighth component of complement, is located on mouse chromosome 4. Immunogenetics 33:18‐23.
   Tarakhovsky, A., Turner, M., Schaal, S., Mee, P.J., Duddy, L.P., Rajewsky, K., and Tybulewicz, V.L.J. 1995. Defective antigen receptor–mediated proliferation of B and T cells in the absence of Vav. Nature 374:467‐470.
   Teh, H.S., Kishi, H., Scott, B., and von Boehmer, H. 1989. Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules. J. Exp. Med. 169:795‐806.
   Theofilopoulos, A.N. and Dixon, F.J. 1985. Murine models of systemic lupus erythematosus. Adv. Immunol. 37:269‐389.
   Todd, J.A., Aitman, T.J., Cornall, R.J., Ghosh, S., Hall, J.R.S., Hearne, C.M., Knight, A.M., Love, J.M., McAleer, J.A., Prins, J., Rodrigues, N., Lathrop, M., Pressey, A., DeLarato, N.H., Peterson, L.B., and Wicker, L.S. 1991. Genetic analysis of autoimmune type 1 diabetes in mice. Nature 351:542‐547.
   Tsui, H.W., Siminovitch, K.A., de Souza, L., and Tsui, F.W. 1993. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nature Genet. 4:124‐129.
   Tublewicz, V.L., Crawford, C.E., Jackson, P.K., Bronson, R.T., and Mulligan, R.C. 1991. Neonatal lethality and lymphopenia in mice with homozygous disruption of the c‐abl proto‐oncogene. Cell 65:1153‐1163.
   Urbanek, P., Weng, Z., Getka, I., Wagner, E.F., and Busslinger, M. 1994. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell 79:901‐912.
   van Kaer, L., Ashton‐Rickardt, P.G., Ploegh, H.L., and Tonegawa, S. 1993. TAP‐1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4−CD8+ cells. Cell 71:1205‐1214.
   Veis, D.J., Sorenson, C.M., Shutter, J.R., and Korsmeyer, S.J. 1993. Bcl‐2‐deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229‐240.
   Verbeek, S., Izon, D., Hofhuis, F., Robanus‐Maandag, E., te Riele, H., van de Wetering, M., Oosterwegel, M., Wilson, A., MacDonald, H.R., and Clevers, H. 1995. An HMG‐box‐containing T‐cell factor required for thymocyte differentiation. Nature 374:70‐74.
   Viney, J.L., Dianda, L., Roberts, S.J., Wen, L., Mallick, C.A., Hayday, A.C., and Owen, M.J. 1994. Lymphocyte proliferation in mice congenitally deficient in T‐cell receptor αβ+ cells. Proc. Natl. Acad. Sci. U.S.A. 91:11948‐11952.
   Viville, S., Neefjes, J., Lotteau, V., Dierich, A., Lemeur, M., Ploegh, H., Benoist, C., and Mathis, D. 1993. Mice lacking the MHC class II–associated invariant chain. Cell 72:635‐648.
   Walker, S.E., Gray, R.H., Fulton, M., Wigley, R.D., and Schnitzer, B. 1978. Palmerston North mice, a new animal model of systemic lupus erythematosus. J. Lab. Clin. Med. 92:932‐945.
   Watanabe, T., Sakai, Y., Miyawaki, S., Shimizu, A., Koiwai, O., and Ohno, K. 1991. A molecular genetic linkage map of mouse chromosome 19, including the lpr, Ly‐44, and TdT genes. Biochem. Genet. 29:325‐336.
   Watanabe‐Fukunaga, R., Brannan, C.I., Copeland, N.G., Jenkins, N.A., and Nagata, S. 1992. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314‐317.
   Wei, X.‐Q., Charles, I.G., Smith, A., Ure, J., Feng, G.‐J., Huang, F.‐P., Xu, D., Muller, W., Moncada, S., and Liew, F.Y. 1995. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375:408‐411.
   Wheat, W.H., Wetsel, R., Falus, A., Tack, B.F., and Strunk, R.C. 1987. The fifth component of complement (C5) in the mouse. Analysis of the molecular basis for deficiency. J. Exp. Med. 165:1442‐1447.
   Wilson, R.W., Ballantyne, C.M., Smith, C.W., Montgomery, C., Bradley, A., O'Brien, W.S., and Beaudet, A.L. 1993. Gene targeting yields a CD18‐mutant mouse for study of inflammation. J. Immunol. 151:1571‐1578.
   Xu, J., Foy, T.M., Laman, J.D., Elliott, E.A., Dunn, J.J., Waldschmidt, T.J., Elsemore, J., Noelle, R.J., and Flavell, R.A. 1994. Mice deficient for the CD40 ligand. Immunity 1:423‐431.
   Yoshikai, Y., Reis, M.D., and Mak, T.W. 1986. Athymic mice express a high level of functional γ‐chain but greatly reduced levels of α‐ and β‐chain T‐cell receptor messages. Nature 324:482‐485.
   Yen, T.T., Gill, A.M., Frigeri, L.G., Barsh, G.S., and Wolff, G.L. 1994. Obesity, diabetes, and neoplasia in yellow (Avy/− mice: Ectopic expression of the agouti gene. FASEB J. 8:479‐488.
   Zhang, R., Alt, F.W., Davidson, L., Orkin, S.H., and Swat, W. 1995. Defective signalling through the T‐ and B‐cell antigen receptors in lymphoid cells lacking the vav proto‐oncogene. Nature 374:470‐473.
   Zhuang, Y., Soriano, P., and Weintraub, H. 1994. The helix‐loop‐helix gene E2A is required for B cell formation. Cell 79:875‐884.
   Zijlstra, M., Bix, M., Simister, N.E., Lorinf, J.M., Raulet, D.H., and Jaenisch, R. 1990. Beta 2‐microglobulin deficient mice lack CD4− CD8− cytolytic T cells. Nature 344:709‐711.
   Zou, Y.R., Takeda, S., and Rajewsky, K. 1993. Gene targeting in the Ig kappa locus: Efficient generation of lambda chain–expressing B cells, independent of gene rearrangements in Ig kappa. EMBO J. 12:811‐820.
   Zsebo, K.M., Williams, D.A., Geissler, E.N., Broudy, V.C., Martin, F.H., Atkins, H.L., Hsu, R.Y., Birkett, N.C., Okino, K.H., Langley, K.E., Smith, K.A., Takeishi, T., Cattanach, B.M., Galli, S.J., and Suggs, S.V. 1990. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c‐kit tyrosine kinase receptor. Cell 63:213‐224.
PDF or HTML at Wiley Online Library