{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:45:36Z","timestamp":1791294336227,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Development of a small animal model for the in vivo study of human immunity and infectious disease remains an important goal, particularly for investigations of HIV vaccine development. NOD\/Lt mice homozygous for the severe combined immunodeficiency (Prkdcscid) mutation readily support engraftment with high levels of human hematolymphoid cells. However, NOD\/LtSz-scid mice are highly radiosensitive, have short life spans, and a small number develop functional lymphocytes with age. To overcome these limitations, we have backcrossed the null allele of the recombination-activating gene (Rag1) for 10 generations onto the NOD\/LtSz strain background. Mice deficient in RAG1 activity are unable to initiate V(D)J recombination in Ig and TCR genes and lack functional T and B lymphocytes. NOD\/LtSz-Rag1null mice have an increased mean life span compared with NOD\/LtSz-scid mice due to a later onset of lymphoma development, are radioresistant, and lack serum Ig throughout life. NOD\/LtSz-Rag1null mice were devoid of mature T or B cells. Cytotoxic assays demonstrated low NK cell activity. NOD\/LtSz-Rag1null mice supported high levels of engraftment with human lymphoid cells and human hemopoietic stem cells. The engrafted human T cells were readily infected with HIV. Finally, NOD\/LtSz-Rag1null recipients of adoptively transferred spleen cells from diabetic NOD\/Lt+\/+ mice rapidly developed diabetes. These data demonstrate the advantages of NOD\/LtSz-Rag1null mice as a radiation and lymphoma-resistant model for long-term analyses of engrafted human hematolymphoid cells or diabetogenic NOD lymphoid cells.<\/jats:p>","DOI":"10.4049\/jimmunol.164.5.2496","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T19:48:34Z","timestamp":1398109714000},"page":"2496-2507","source":"Crossref","is-referenced-by-count":138,"title":["NOD\/LtSz-\n                    <i>Rag1<\/i>\n                    <i>null<\/i>\n                    Mice: An Immunodeficient and Radioresistant Model for Engraftment of Human Hematolymphoid Cells, HIV Infection, and Adoptive Transfer of NOD Mouse Diabetogenic T Cells"],"prefix":"10.1093","volume":"164","author":[{"given":"Leonard D","family":"Shultz","sequence":"first","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A","family":"Lang","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri W","family":"Christianson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Gott","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Lyons","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syuji","family":"Umeda","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Leiter","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RuthAnn","family":"Hesselton","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, University of Massachusetts Medical Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J","family":"Wagar","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, University of Massachusetts Medical Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean H","family":"Leif","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, University of Massachusetts Medical Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O\u0301rit","family":"Kollet","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Weizmann Institute of Science , Rehovot ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsvee","family":"Lapidot","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Weizmann Institute of Science , Rehovot ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale L","family":"Greiner","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, University of Massachusetts Medical Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,3,1]]},"reference":[{"key":"2026020213162059800_R1","first-page":"774","volume-title":"J. Infect. Dis.","year":"1995"},{"key":"2026020213162059800_R2","first-page":"399","volume-title":"Annu. Rev. Immunol.","year":"1991"},{"key":"2026020213162059800_R3","first-page":"256","volume-title":"Nature","year":"1988"},{"key":"2026020213162059800_R4","first-page":"1137","volume-title":"Science","year":"1992"},{"key":"2026020213162059800_R5","first-page":"1632","volume-title":"Science","year":"1988"},{"key":"2026020213162059800_R6"},{"key":"2026020213162059800_R7","first-page":"180","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020213162059800_R8","first-page":"888","volume-title":"Am. J. Pathol.","year":"1995"},{"key":"2026020213162059800_R9","first-page":"166","volume-title":"Stem Cells","year":"1998"},{"key":"2026020213162059800_R10","first-page":"15","volume-title":"Biol. Blood Marrow Transplant.","year":"1996"},{"key":"2026020213162059800_R11","first-page":"3578","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020213162059800_R12","first-page":"186","volume-title":"Cell. Immunol.","year":"1996"},{"key":"2026020213162059800_R13","first-page":"163","volume-title":"Hum. Mol. Genet.","year":"1995"},{"key":"2026020213162059800_R14","first-page":"3731","volume-title":"Blood","year":"1996"},{"key":"2026020213162059800_R15","first-page":"85","volume-title":"Blood","year":"1997"},{"key":"2026020213162059800_R16","first-page":"4307","volume-title":"Blood","year":"1997"},{"key":"2026020213162059800_R17","first-page":"332","volume-title":"Exp. Hematol.","year":"1998"},{"key":"2026020213162059800_R18","first-page":"845","volume-title":"Science","year":"1999"},{"key":"2026020213162059800_R19","first-page":"3290","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1992"},{"key":"2026020213162059800_R20","first-page":"869","volume-title":"Cell","year":"1992"},{"key":"2026020213162059800_R21","first-page":"855","volume-title":"Cell","year":"1992"},{"key":"2026020213162059800_R22","first-page":"716","volume-title":"J. Clin. Endocrinol. Metab.","year":"1994"},{"key":"2026020213162059800_R23","first-page":"607","volume-title":"Scand. J. Immunol.","year":"1995"},{"key":"2026020213162059800_R24","first-page":"39","volume-title":"Cytogenet. Cell Genet.","year":"1992"},{"key":"2026020213162059800_R25","first-page":"479","volume-title":"Nature","year":"1990"},{"key":"2026020213162059800_R26","first-page":"1394","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1991"},{"key":"2026020213162059800_R27","first-page":"4061","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1991"},{"key":"2026020213162059800_R28","first-page":"10838","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026020213162059800_R29","first-page":"63","volume-title":"Immunol. Rev.","year":"1979"},{"key":"2026020213162059800_R30","first-page":"5","volume-title":"Immunol. Rev.","year":"1982"},{"key":"2026020213162059800_R31","first-page":"317","volume-title":"J. Immunol.","year":"1981"},{"key":"2026020213162059800_R32","first-page":"115","volume-title":"Curr. Top. Microbiol. Immunol.","year":"1978"},{"key":"2026020213162059800_R33","volume-title":"Histopathology Technique and Practical Histochemistry","year":"1954"},{"key":"2026020213162059800_R34","first-page":"863","volume-title":"Cell","year":"1990"},{"key":"2026020213162059800_R35","first-page":"923","volume-title":"Blood","year":"1999"},{"key":"2026020213162059800_R36","first-page":"630","volume-title":"J. Infect. Dis.","year":"1993"},{"key":"2026020213162059800_R37","first-page":"279","volume-title":"AIDS Res. Hum. Retroviruses","year":"1994"},{"key":"2026020213162059800_R38","first-page":"44","volume-title":"Diabetes","year":"1993"},{"key":"2026020213162059800_R39","first-page":"1517","volume-title":"Science","year":"1990"},{"key":"2026020213162059800_R40","first-page":"603","volume-title":"Curr. Opin. Genet. Dev.","year":"1996"},{"key":"2026020213162059800_R41","first-page":"1178","volume-title":"Science","year":"1995"},{"key":"2026020213162059800_R42","first-page":"79","volume-title":"Curr. Top. Microbiol. Immunol.","year":"1996"},{"key":"2026020213162059800_R43","first-page":"10792","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1995"},{"key":"2026020213162059800_R44","first-page":"3806","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020213162059800_R45","first-page":"251","volume-title":"Curr. Top. Microbiol. Immunol.","year":"1989"},{"key":"2026020213162059800_R46","first-page":"3305","volume-title":"J. Immunol.","year":"1990"},{"key":"2026020213162059800_R47","first-page":"481","volume-title":"Int. J. Cancer","year":"1990"},{"key":"2026020213162059800_R48","first-page":"1392","volume-title":"Diabetes","year":"1995"},{"key":"2026020213162059800_R49","first-page":"525","volume-title":"Scand. J. Immunol.","year":"1996"},{"key":"2026020213162059800_R50","first-page":"109","volume-title":"Leukemia","year":"1997"},{"key":"2026020213162059800_R51"},{"key":"2026020213162059800_R52","first-page":"323","volume-title":"Annu. Rev. Immunol.","year":"1991"},{"key":"2026020213162059800_R53","first-page":"1016","volume-title":"J. Exp. Med.","year":"1988"},{"key":"2026020213162059800_R54","first-page":"3912","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020213162059800_R55","first-page":"2049","volume-title":"J. Exp. Med.","year":"1996"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/164\/5\/2496\/62140945\/2496.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/164\/5\/2496\/62140945\/2496.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:26:50Z","timestamp":1770056810000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/164\/5\/2496\/8039492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,3,1]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2000,3,1]]},"published-print":{"date-parts":[[2000,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.164.5.2496","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2000,3]]},"published":{"date-parts":[[2000,3,1]]}}}