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dc.contributor.authorShultz, Leonard D.
dc.contributor.authorLang, Pamela A.
dc.contributor.authorChristianson, Sherri W.
dc.contributor.authorGott, Bruce
dc.contributor.authorLyons, Bonnie L.
dc.contributor.authorUmeda, Syuji
dc.contributor.authorLeiter, Edward H.
dc.contributor.authorHesselton, RuthAnn M.
dc.contributor.authorWagar, Eric J.
dc.contributor.authorLeif, Jean H.
dc.contributor.authorKollet, Orit
dc.contributor.authorLapidot, Tsvee
dc.contributor.authorGreiner, Dale L.
dc.date2022-08-11T08:08:48.000
dc.date.accessioned2022-08-23T16:08:51Z
dc.date.available2022-08-23T16:08:51Z
dc.date.issued2000-02-29
dc.date.submitted2008-12-11
dc.identifier.citation<p>J Immunol. 2000 Mar 1;164(5):2496-507.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.doi10.4049/jimmunol.164.5.2496
dc.identifier.pmid10679087
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32549
dc.description.abstractDevelopment 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10679087&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.4049/jimmunol.164.5.2496
dc.subject*Adoptive Transfer; Aging; Animals; Diabetes Mellitus, Type 1; Disease Models, Animal; Erythrocyte Count; Female; Fetal Blood; Genes, RAG-1; HIV Infections; *Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins; Immunologic Deficiency; Syndromes; Immunophenotyping; Killer Cells, Natural; Leukocyte Count; Leukocytes, Mononuclear; Longevity; Lymphoid Tissue; Lymphoma; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Poly I-C; Radiation Tolerance; Spleen; T-Lymphocytes
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleNOD/LtSz-Rag1null mice: an immunodeficient and radioresistant model for engraftment of human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume164
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1113
dc.identifier.contextkey680286
html.description.abstract<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.</p>
dc.identifier.submissionpathgsbs_sp/1113
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages2496-507


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