{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:16:29Z","timestamp":1791411389846,"version":"4.3.3"},"reference-count":56,"publisher":"Cold Spring Harbor Laboratory","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1994,4,1]]},"abstract":"<jats:p>The bmi-1 proto-oncogene has been implicated in B-cell lymphomagenesis in E mu-myc transgenic mice. Distinct domains of the Bmi-1 protein are highly conserved within the Drosophila protein Posterior Sex Combs, a member of the Polycomb group involved in maintaining stable repression of homeotic genes during development. We have inactivated the bmi-1 gene in the germ line of mice by homologous recombination in ES cells. Null mutant mice display three phenotypic alterations: (1) a progressive decrease in the number of hematopoietic cells and an impaired proliferative response of these cells to mitogens; (2) neurological abnormalities manifested by an ataxic gait and sporadic seizures; and (3) posterior transformation, in most cases along the complete anteroposterior axis of the skeleton. The observations indicate that Mbi-1 plays an important role in morphogenesis during embryonic development and in hematopoiesis throughout pre- and postnatal life. Furthermore, these data provide the first evidence of functional conservation of a mammalian Polycomb group homolog.<\/jats:p>","DOI":"10.1101\/gad.8.7.757","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:15:46Z","timestamp":1181078146000},"page":"757-769","source":"Crossref","is-referenced-by-count":678,"title":["Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene."],"prefix":"10.1101","volume":"8","author":[{"given":"N M","family":"van der Lugt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Domen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Linders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"van Roon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Robanus-Maandag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"te Riele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"van der Valk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Deschamps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sofroniew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"van Lohuizen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1994,4,1]]},"reference":[{"key":"2021111418140033000_8.7.757.1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.1020100314"},{"key":"2021111418140033000_8.7.757.2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.1020120504"},{"key":"2021111418140033000_8.7.757.3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.3.1016"},{"key":"2021111418140033000_8.7.757.4","doi-asserted-by":"publisher","DOI":"10.1038\/353351a0"},{"key":"2021111418140033000_8.7.757.5","doi-asserted-by":"publisher","DOI":"10.1038\/350473a0"},{"key":"2021111418140033000_8.7.757.6","doi-asserted-by":"publisher","DOI":"10.1038\/355516a0"},{"key":"2021111418140033000_8.7.757.7","doi-asserted-by":"publisher","DOI":"10.1038\/356612a0"},{"key":"2021111418140033000_8.7.757.8","first-page":"117","article-title":"Mammalian homeobox genes in normal development and neoplasia.","volume":"3","year":"1992","journal-title":"Crit. Rev. Oncogenesis"},{"key":"2021111418140033000_8.7.757.9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.5.1665"},{"key":"2021111418140033000_8.7.757.10","first-page":"347","article-title":"Growth retardation, high mortality and low reproductivity of neurological mutant mice.","volume":"181","year":"1975","journal-title":"Anat. Rec."},{"key":"2021111418140033000_8.7.757.11","doi-asserted-by":"crossref","unstructured":"Dung, H.C. 1981. Lethargic mice. In Immunological defects in laboratory animals (ed. M.E. Gershwin and B. Merchant) vol. 2, pp. 17\u201337. Plenum Press, New York.","DOI":"10.1007\/978-1-4684-8652-0_2"},{"key":"2021111418140033000_8.7.757.12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1365-2990.1977.tb00575.x","article-title":"Polyneuropathies and CNS protein metabolism. I. Description of the acrylamide syndrome in rats.","volume":"3","year":"1977","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2021111418140033000_8.7.757.13","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90106-9"},{"key":"2021111418140033000_8.7.757.14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.1.257"},{"key":"2021111418140033000_8.7.757.15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.5.1213"},{"key":"2021111418140033000_8.7.757.16","first-page":"17","article-title":"Nucleotide sequence of bup, an upstream gene in the bmi-1 proviral insertion locus.","volume":"17","year":"1992","journal-title":"Mol. Biol. Rep."},{"key":"2021111418140033000_8.7.757.17","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90383-A"},{"key":"2021111418140033000_8.7.757.18","doi-asserted-by":"publisher","DOI":"10.1038\/326292a0"},{"key":"2021111418140033000_8.7.757.19","doi-asserted-by":"publisher","DOI":"10.1177\/29.4.6166661"},{"key":"2021111418140033000_8.7.757.20","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90387-R"},{"key":"2021111418140033000_8.7.757.21","doi-asserted-by":"publisher","DOI":"10.1038\/316153a0"},{"key":"2021111418140033000_8.7.757.22","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(72)90176-7"},{"key":"2021111418140033000_8.7.757.23","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90574-I"},{"key":"2021111418140033000_8.7.757.24","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90810-2"},{"key":"2021111418140033000_8.7.757.25","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.07.040189.000551"},{"key":"2021111418140033000_8.7.757.26","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1182\/blood.V80.10.2445.2445","article-title":"Homeobox genes in normal hematopoiesis and leukemia.","volume":"80","year":"1992","journal-title":"Blood"},{"key":"2021111418140033000_8.7.757.27","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.4049\/jimmunol.142.11.3875","article-title":"Normal B-cell precursors responsive to recombinant murine IL-7 and inhibition of IL-7 activity by transforming growth factor-\u03b2.","volume":"142","year":"1989","journal-title":"J. Immunol."},{"key":"2021111418140033000_8.7.757.28","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90406-3"},{"key":"2021111418140033000_8.7.757.29","doi-asserted-by":"publisher","DOI":"10.1038\/276565a0"},{"key":"2021111418140033000_8.7.757.30","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(91)90011-O"},{"key":"2021111418140033000_8.7.757.31","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90034-V"},{"key":"2021111418140033000_8.7.757.32","doi-asserted-by":"publisher","DOI":"10.1038\/359835a0"},{"key":"2021111418140033000_8.7.757.33","unstructured":"Lyon, M.F. and A.G. Searle, eds. 1989. Genetic variants and strains of the laboratory mouse, 2nd ed, Oxford University Press, Oxford, England."},{"key":"2021111418140033000_8.7.757.34","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1242\/dev.117.2.641","article-title":"The Polycomb group gene Posterior Sex Combs encodes a chromosomal protein.","volume":"117","year":"1993","journal-title":"Development"},{"key":"2021111418140033000_8.7.757.35","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90471-N"},{"key":"2021111418140033000_8.7.757.36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0925-4773(92)90021-B","article-title":"Ectopic expression of Hox2.3 induces craniofacial and skeletal malformations in transgenic mice.","volume":"39","year":"1992","journal-title":"Mech. Dev."},{"key":"2021111418140033000_8.7.757.37","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.4049\/jimmunol.146.11.3785","article-title":"The role of recombinant stem cell factor in early B cell development.","volume":"146","year":"1991","journal-title":"J. Immunol."},{"key":"2021111418140033000_8.7.757.38","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90303-N"},{"key":"2021111418140033000_8.7.757.39","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90388-S"},{"key":"2021111418140033000_8.7.757.40","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90229-J"},{"key":"2021111418140033000_8.7.757.41","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90588-4"},{"key":"2021111418140033000_8.7.757.42","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(87)90132-1"},{"key":"2021111418140033000_8.7.757.43","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240210206"},{"key":"2021111418140033000_8.7.757.44","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.4049\/jimmunol.146.9.3068","article-title":"IL-7 maintains the T cell precursor potential of CD4-\/CD8-\/CD3- thymocytes.","volume":"146","year":"1991","journal-title":"J. Immunol."},{"key":"2021111418140033000_8.7.757.45","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1182\/blood.V74.6.1936.1936","article-title":"A stimulatory effect of recombinant interleukin-7 on B-cell colony formation and an inhibitory effect of interleukin-1\u03b1.","volume":"74","year":"1989","journal-title":"Blood"},{"key":"2021111418140033000_8.7.757.46","doi-asserted-by":"crossref","first-page":"20021","DOI":"10.1016\/S0021-9258(17)45476-7","article-title":"Expression of a novel DNA-binding protein with zinc finger structure in various tumor cells.","volume":"265","year":"1990","journal-title":"J. Biol. Chem."},{"key":"2021111418140033000_8.7.757.47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1182\/blood.V43.1.33.33","article-title":"Induction of sustained hemopoiesis in fatty marrow.","volume":"43","year":"1974","journal-title":"Blood"},{"key":"2021111418140033000_8.7.757.48","doi-asserted-by":"publisher","DOI":"10.1038\/348649a0"},{"key":"2021111418140033000_8.7.757.49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.11.5128"},{"key":"2021111418140033000_8.7.757.50","doi-asserted-by":"publisher","DOI":"10.1084\/jem.154.5.1517"},{"key":"2021111418140033000_8.7.757.51","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90382-9"},{"key":"2021111418140033000_8.7.757.52","doi-asserted-by":"publisher","DOI":"10.1038\/353353a0"},{"key":"2021111418140033000_8.7.757.53","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1242\/dev.110.4.1159","article-title":"Expression of the murine homeobox-containing gene hox-2.3 suggests multiple time-dependent and tissue-specific roles during development.","volume":"110","year":"1990","journal-title":"Development"},{"key":"2021111418140033000_8.7.757.54","doi-asserted-by":"publisher","DOI":"10.1038\/360741a0"},{"key":"2021111418140033000_8.7.757.55","doi-asserted-by":"publisher","DOI":"10.1007\/BF00332424"},{"key":"2021111418140033000_8.7.757.56","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/j.1460-2075.1991.tb07931.x","article-title":"Direct interaction of the Polycomb protein with Antennapedia regulatory sequences in polytene chromosomes of Drosophila melanogaster.","volume":"10","year":"1991","journal-title":"EMBO J."}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.8.7.757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T06:25:41Z","timestamp":1683872741000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.8.7.757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4,1]]},"references-count":56,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1994,4,1]]}},"alternative-id":["10.1101\/gad.8.7.757"],"URL":"https:\/\/doi.org\/10.1101\/gad.8.7.757","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4,1]]}}}