{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:17:05Z","timestamp":1789823825565,"version":"4.0.1"},"reference-count":54,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,8,29]]},"abstract":"<jats:p>The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant mammalian tyrosine phosphatases in hematopoietic cells; however, its role in hematopoietic cell function remains unknown. In this report, we investigated the physiological function(s) of TC-PTP by generating TC-PTP\u2013deficient mutant mice. The three genotypes (+\/+, +\/\u2212, \u2212\/\u2212) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3\u20135 wk of age, displaying runting, splenomegaly, and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell functions. However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected. BM transplantation experiments showed that hematopoietic failure in TC-PTP \u2212\/\u2212 animals was not due to a stem cell defect, but rather to a stromal cell deficiency. This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.<\/jats:p>","DOI":"10.1084\/jem.186.5.683","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:49:30Z","timestamp":1027687770000},"page":"683-693","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":318,"title":["Impaired Bone Marrow Microenvironment and Immune Function in T Cell Protein Tyrosine Phosphatase\u2013deficient Mice"],"prefix":"10.1084","volume":"186","author":[{"given":"Kong E.","family":"You-Ten","sequence":"first","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Muise","sequence":"additional","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Iti\u00e9","sequence":"additional","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Michaliszyn","sequence":"additional","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Wagner","sequence":"additional","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Jothy","sequence":"additional","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne S.","family":"Lapp","sequence":"additional","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel L.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"From the *Department of Biochemistry, \u2021Department of Pathology, and \u00a7Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,8,29]]},"reference":[{"key":"2023072507384526000_B1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1182\/blood.V83.2.361.361","article-title":"Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates","volume":"83","author":"Funk","year":"1994","journal-title":"Blood"},{"key":"2023072507384526000_B2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0167-5699(95)80096-4","article-title":"A signalling pathway governing early thymocyte maturation","volume":"16","author":"Anderson","year":"1995","journal-title":"Immunol Today"},{"key":"2023072507384526000_B3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev.immunol.14.1.131","article-title":"Genetic analysis of tyrosine kinase funtion in B cell development","volume":"14","author":"Satterthwaite","year":"1996","journal-title":"Annu Rev Immunol"},{"key":"2023072507384526000_B4","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1006\/cimm.1996.0220","article-title":"Abnormal peripheral lymphocyte function in c-abl mutant mice","volume":"172","author":"Hardin","year":"1996","journal-title":"Cell Immunol"},{"key":"2023072507384526000_B5","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/0092-8674(91)90012-N","article-title":"Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations","volume":"65","author":"Schwartzberg","year":"1991","journal-title":"Cell"},{"key":"2023072507384526000_B6","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/0092-8674(91)90011-M","article-title":"Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene","volume":"65","author":"Tybulewicz","year":"1991","journal-title":"Cell"},{"key":"2023072507384526000_B7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1146\/annurev.iy.12.040194.000505","article-title":"CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development","volume":"12","author":"Trowbridge","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"2023072507384526000_B8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1615\/CritRevImmunol.v14.i3-4.50","article-title":"The role of protein tyrosine phosphatases in lymphocyte activation and differentiation","volume":"14","author":"Yakura","year":"1994","journal-title":"Crit Rev Immunol"},{"key":"2023072507384526000_B9","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1084\/jem.183.4.1707","article-title":"CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+thymocytes, and B cell maturation","volume":"183","author":"Byth","year":"1996","journal-title":"J Exp Med"},{"key":"2023072507384526000_B10","first-page":"1651","article-title":"Differential effects of expression of the CD45 tyrosine protein phosphatase on the tyrosine phosphorylation of the lck, fyn and c-srctyrosine protein kinases","volume":"13","author":"Hurley","year":"1993","journal-title":"Mol Cell Biol"},{"key":"2023072507384526000_B11","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/ng0693-124","article-title":"Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene","volume":"4","author":"Tsui","year":"1993","journal-title":"Nat Genet"},{"key":"2023072507384526000_B12","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/0092-8674(93)90369-2","article-title":"Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene","volume":"73","author":"Shultz","year":"1993","journal-title":"Cell"},{"key":"2023072507384526000_B13","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1073\/pnas.86.14.5257","article-title":"cDNA isolation from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family","volume":"86","author":"Cool","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507384526000_B14","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1073\/pnas.89.2.499","article-title":"Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase","volume":"89","author":"Mosinger","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507384526000_B15","first-page":"1203","article-title":"Activation of transcription via AP-1 or CREB regulatory sites is blocked by protein tyrosine phosphatases","volume":"6","author":"Champion-Arnaud","year":"1991","journal-title":"Oncogene"},{"key":"2023072507384526000_B16","doi-asserted-by":"crossref","first-page":"26755","DOI":"10.1074\/jbc.271.43.26755","article-title":"Two splice variants of a tyrosine phosphatase differ in substrate specificity, DNA binding, and subcellular location","volume":"271","author":"Kamatkar","year":"1996","journal-title":"J Biol Chem"},{"key":"2023072507384526000_B17","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1083\/jcb.131.3.631","article-title":"COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus","volume":"131","author":"Lorenzen","year":"1995","journal-title":"J Cell Biol"},{"key":"2023072507384526000_B18","first-page":"3030","article-title":"Nuclear localization and cell cycle regulation of a murine protein tyrosine phosphatase","volume":"14","author":"Tillman","year":"1994","journal-title":"Mol Cell Biol"},{"key":"2023072507384526000_B19","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/glia.440090409","article-title":"Differential intracellular compartmentalization of phosphotyrosine phosphatases in a glial cell line: TC-PTP versus PTP-1B","volume":"9","author":"Faure","year":"1993","journal-title":"GLIA"},{"key":"2023072507384526000_B20","doi-asserted-by":"crossref","first-page":"7280","DOI":"10.1073\/pnas.87.18.7280","article-title":"Expression of a human T-cell protein tyrosine-phosphatase in baby hamster kidney cells","volume":"87","author":"Cool","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507384526000_B21","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.1021\/bi00242a022","article-title":"Purification and characterization of a human recombinant T-cell protein-tyrosine-phosphatase from a baculovirus expression system","volume":"30","author":"Zander","year":"1991","journal-title":"Biochemistry"},{"key":"2023072507384526000_B22","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1126\/science.1703321","article-title":"Complementation of the mitotic activator, p80cdc25, by a human protein-tyrosine phosphatase","volume":"250","author":"Gould","year":"1990","journal-title":"Science (Wash DC)"},{"key":"2023072507384526000_B23","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1006\/geno.1995.1181","article-title":"Structure of the murine MPTP-PEST gene: genomic organization and chromosomal mapping","volume":"28","author":"Charest","year":"1995","journal-title":"Genomics"},{"key":"2023072507384526000_B24"},{"key":"2023072507384526000_B25","doi-asserted-by":"crossref","first-page":"9929","DOI":"10.1073\/pnas.89.20.9929","article-title":"Targeting of the T-cell receptor \u03b6-chain gene in embryonic stem cells: strategies for generating multiple mutations in a single gene","volume":"89","author":"Love","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507384526000_B26","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1084\/jem.182.3.655","article-title":"The Ity\/Lsh\/Bcglocus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene","volume":"182","author":"Vidal","year":"1995","journal-title":"J Exp Med"},{"key":"2023072507384526000_B27","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/0092-8674(92)90611-F","article-title":"Targeted mutation of the DNA methyltransferase gene results in embryonic lethality","volume":"69","author":"Li","year":"1992","journal-title":"Cell"},{"key":"2023072507384526000_B28"},{"key":"2023072507384526000_B29","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1073\/pnas.81.7.1991","article-title":"Genomic sequencing","volume":"81","author":"Church","year":"1984","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507384526000_B30","first-page":"532","article-title":"A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples","volume":"15","author":"Chomczynski","year":"1993","journal-title":"Biotechniques"},{"key":"2023072507384526000_B31","doi-asserted-by":"crossref","first-page":"6951","DOI":"10.1093\/nar\/12.18.6951","article-title":"Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues","volume":"12","author":"Piechaczyk","year":"1984","journal-title":"Nucleic Acids Res"},{"key":"2023072507384526000_B32","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4049\/jimmunol.155.1.172","article-title":"Induction of a glucocorticoid-sensitive F1-antiparental mechanism that affects engraftment during graft-versus-host disease","volume":"155","author":"You-Ten","year":"1995","journal-title":"J Immunol"},{"key":"2023072507384526000_B33","first-page":"599","article-title":"Further improvements in the plaque technique for detecting single antibody-forming cells","volume":"14","author":"Cunningham","year":"1968","journal-title":"Immunology"},{"key":"2023072507384526000_B34","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/00007890-199101000-00044","article-title":"T cell subsets in the thymus of graft-versus-host immunosuppressed mice","volume":"51","author":"Kornbluth","year":"1991","journal-title":"Transplantation (Baltimore)"},{"key":"2023072507384526000_B35","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1002\/eji.1830210912","article-title":"Hemolytic anemia in non-obese diabetic mice","volume":"21","author":"Baxter","year":"1991","journal-title":"Eur J Immunol"},{"key":"2023072507384526000_B36","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/1074-7613(94)90065-5","article-title":"T cell antigen receptor signaling: three families of tyrosine kinases and a phosphatase","volume":"1","author":"Mustelin","year":"1994","journal-title":"Immunity"},{"key":"2023072507384526000_B37","doi-asserted-by":"crossref","first-page":"7410","DOI":"10.1073\/pnas.88.16.7410","article-title":"Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases","volume":"88","author":"Burkhardt","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507384526000_B38","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1126\/science.1702903","article-title":"Association of B cell antigen receptor with protein tyrosine kinase Lyn","volume":"251","author":"Yamanashi","year":"1991","journal-title":"Science (Wash DC)"},{"key":"2023072507384526000_B39","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1073\/pnas.90.4.1402","article-title":"Correlation between Src family member regulation by the protein-tyrosine-phosphatase CD45 and transmembrane signaling through the T cell receptor","volume":"90","author":"Cahir McFarland, E.D., T.R. Hurley, J.T. Pingel, B.M. Sefton, A. Shaw, and M.L. Thomas","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507384526000_B40","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0167-5699(94)90268-2","article-title":"Regulation of B-cell activation by CD45: a question of mechanism","volume":"15","author":"Justement","year":"1994","journal-title":"Immunol Today"},{"key":"2023072507384526000_B41","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1126\/science.7716523","article-title":"Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by FcRIIB1","volume":"268","author":"D'Ambrosio","year":"1995","journal-title":"Science (Wash DC)"},{"key":"2023072507384526000_B42","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1126\/science.272.5265.1170","article-title":"Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4","volume":"272","author":"Marengere","year":"1996","journal-title":"Science (Wash DC)"},{"key":"2023072507384526000_B43","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/352736a0","article-title":"A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases","volume":"352","author":"Shen","year":"1991","journal-title":"Nature (Lond)"},{"key":"2023072507384526000_B44","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/j.1432-1033.1996.0736p.x","article-title":"Involvement of Src-homology-2-domain\u2013containing protein-tyrosine phosphatase 2 in T cell activation","volume":"237","author":"Tailor","year":"1996","journal-title":"Eur J Biochem"},{"key":"2023072507384526000_B45","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.4049\/jimmunol.153.6.2381","article-title":"B cell Ag receptor mediates different types of signals in the protein kinase activity between immature B cell and mature B cell","volume":"153","author":"Igarashi","year":"1994","journal-title":"J Immunol"},{"key":"2023072507384526000_B46","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1146\/annurev.iy.10.040192.003551","article-title":"","volume":"10","author":"Ikuta","year":"1992","journal-title":"Annu Rev Immunol"},{"key":"2023072507384526000_B47","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1146\/annurev.iy.08.040190.000551","article-title":"Regulation of hemopoiesis by bone marrow stromal cells and their products","volume":"8","author":"Dorshkind","year":"1990","journal-title":"Annu Rev Immunol"},{"key":"2023072507384526000_B48","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/352438a0","article-title":"Fibronectin and VLA-4 in hematopoietic stem cell\u2013microenvironment interactions","volume":"352","author":"Williams","year":"1991","journal-title":"Nature (Lond)"},{"key":"2023072507384526000_B49","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1002\/eji.1830201106","article-title":"Microenvironmental organization and stromal cell association of B lymphocyte precursor cells in mouse bone marrow","volume":"20","author":"Jacobsen","year":"1990","journal-title":"Eur J Immunol"},{"key":"2023072507384526000_B50","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1084\/jem.176.4.927","article-title":"Highly restricted expression of a stromal cell determinant in mouse bone marrow in vivo","volume":"176","author":"Jacobsen","year":"1992","journal-title":"J Exp Med"},{"key":"2023072507384526000_B51","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/S0092-8674(00)81301-X","article-title":"Differential requirements for \u03b1-integrins during fetal and adult hematopoiesis","volume":"85","author":"Arroyo","year":"1996","journal-title":"Cell"},{"key":"2023072507384526000_B52","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1084\/jem.178.1.257","article-title":"Inhibition of murine B and T lymphopoiesis in vivo by an anti\u2013interleukin 7 monoclonal antibody","volume":"178","author":"Grabstein","year":"1993","journal-title":"J Exp Med"},{"key":"2023072507384526000_B53","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1182\/blood.V80.5.1218.1218","article-title":"Interleukin-11 stimulates multiple phases of erythropoiesis in vitro","volume":"80","author":"Quesniaux","year":"1992","journal-title":"Blood"},{"key":"2023072507384526000_B54","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.4049\/jimmunol.155.5.2359","article-title":"Stimulation of human bone marrow stromal cell tyrosine kinases and IL-6 production by contact with B lymphocytes","volume":"155","author":"Jarvis","year":"1995","journal-title":"J Immunol"}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/186\/5\/683\/1685856\/97-0656.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/186\/5\/683\/1685856\/97-0656.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T04:22:24Z","timestamp":1690258944000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/186\/5\/683\/7288\/Impaired-Bone-Marrow-Microenvironment-and-Immune"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8,29]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1997,8,29]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.186.5.683","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8,29]]}}}