{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:54:32Z","timestamp":1791255272202,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T00:00:00Z","timestamp":1346803200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>Using N\u2010ethyl\u2010N\u2010nitrosourea\u2010induced mutagenesis, we established a mouse model with a novel form of neutropenia resulting from a point mutation in the transcriptional repressor Growth Factor Independence 1 (Gfi1). These mice, called <jats:italic>Genista<\/jats:italic>, had normal viability and no weight loss, in contrast to mice expressing null alleles of the <jats:italic>Gfi1<\/jats:italic> gene. Furthermore, the <jats:italic>Genista<\/jats:italic> mutation had a very limited impact on lymphopoiesis or on T\u2010 and B\u2010cell function. Within the bone marrow (BM), the <jats:italic>Genista<\/jats:italic> mutation resulted in a slight increase of monopoiesis and in a block of terminal granulopoiesis. This block occurred just after the metamyelocytic stage and resulted in the generation of small numbers of atypical CD11b<jats:sup>+<\/jats:sup>Ly\u20106G<jats:sup>int<\/jats:sup> neutrophils, the nuclear morphology of which resembled that of mature WT neutrophils. Unexpectedly, once released from the BM, these atypical neutrophils contributed to induce mild forms of autoantibody\u2010induced arthritis and of immune complex\u2010mediated lung alveolitis. They additionally failed to provide resistance to acute bacterial infection. Our study demonstrates that a hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia characterized by a split pattern of functional responses, reflecting the distinct thresholds required for eliciting neutrophil\u2010mediated inflammatory and anti\u2010infectious responses.<\/jats:p>","DOI":"10.1002\/eji.201242589","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T06:18:57Z","timestamp":1339395537000},"page":"2395-2408","source":"Crossref","is-referenced-by-count":53,"title":["A hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia"],"prefix":"10.1002","volume":"42","author":[{"given":"Diana","family":"Ordo\u00f1ez\u2010Rueda","sequence":"first","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"J\u00f6nsson","sequence":"additional","affiliation":[{"name":"Institut Pasteur D\u00e9partement d'Immunologie Unit\u00e9 d'Allergologie Mol\u00e9culaire et Cellulaire  Paris France"},{"name":"INSERM  U760 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Mancardi","sequence":"additional","affiliation":[{"name":"Institut Pasteur D\u00e9partement d'Immunologie Unit\u00e9 d'Allergologie Mol\u00e9culaire et Cellulaire  Paris France"},{"name":"INSERM  U760 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Malzac","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinming","family":"Liang","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Bertosio","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Grenot","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Blanquet","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sybille","family":"Sabrautzki","sequence":"additional","affiliation":[{"name":"Hemholtz Zentrum Muenchen Institute of Experimental Genetics  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Hrab\u011b","family":"de Angelis","sequence":"additional","affiliation":[{"name":"Hemholtz Zentrum Muenchen Institute of Experimental Genetics  Munich Germany"},{"name":"Lehrstuhl fuer Experimentelle Genetik Technische Universitaet Muenchen  Freising\u2010Weihenstephan Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"M\u00e9resse","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Duprez","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM) INSERM Institut Paoli\u2010Calmettes, CNRS\u2010UMR7258  U1068 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Bruhns","sequence":"additional","affiliation":[{"name":"Institut Pasteur D\u00e9partement d'Immunologie Unit\u00e9 d'Allergologie Mol\u00e9culaire et Cellulaire  Paris France"},{"name":"INSERM  U760 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Malissen","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Malissen","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille\u2010Luminy Aix\u2010Marseille Universit\u00e9, UM2  Marseille France"},{"name":"INSERM  U1104 Marseille France"},{"name":"CNRS  UMR7280 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2779"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-3346"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2003.09.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3024"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.08.006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2004.12.003"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00501-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng831"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600419"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021417"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608981103"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.moh.0000190111.85284.8f"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27238"},{"key":"e_1_2_7_15_1","first-page":"1","article-title":"Characterization of B lymphopoiesis in mouse bone marrow and spleen","volume":"271","author":"Hardy R. R.","year":"2004","journal-title":"Methods Mol. Biol."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400808200"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0810461"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-259028"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-003-0131-5"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003642"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1004201"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00138"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/315278"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605443103"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.12.020"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1170"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3070"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.8.4450"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2003.12.008"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.8.4475"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111908"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101259"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81989-3"},{"key":"e_1_2_7_34_1","first-page":"1","article-title":"ENU mutagenesis in mice","volume":"415","author":"Georgel P.","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00080-3"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-367334"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201242589","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201242589","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T12:56:44Z","timestamp":1695473804000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201242589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2012,9]]}},"alternative-id":["10.1002\/eji.201242589"],"URL":"https:\/\/doi.org\/10.1002\/eji.201242589","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9]]}}}