{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:00:06Z","timestamp":1789974006611,"version":"4.0.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T00:00:00Z","timestamp":1412812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T00:00:00Z","timestamp":1412812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The pro-apoptotic BH3-only BCL-2 family member BIM is a critical determinant of hematopoietic cell development and homeostasis. It has been argued that the striking hematopoietic abnormalities of BIM-deficient mice (accumulation of lymphocytes and granulocytes) may be the result of the loss of the protein throughout the whole animal rather than a consequence intrinsic to the loss of BIM in hematopoietic cells. To address this issue and allow the deletion of BIM in specific cell types in future studies, we have developed a mouse strain with a conditional\n                    <jats:italic>Bim<\/jats:italic>\n                    allele as well as a new Cre transgenic strain,\n                    <jats:italic>Vav-CreER<\/jats:italic>\n                    , in which the tamoxifen-inducible CreER recombinase (fusion protein) is predominantly expressed in the hematopoietic system. We show that acute loss of BIM in the adult mouse rapidly results in the hematopoietic phenotypes previously observed in mice lacking BIM in all tissues. This includes changes in thymocyte subpopulations, increased white blood cell counts and resistance of lymphocytes to BIM-dependent apoptotic stimuli, such as cytokine deprivation. We have validated this novel conditional\n                    <jats:italic>Bim<\/jats:italic>\n                    knockout mouse model using established and newly developed CreER strains (\n                    <jats:italic>Rosa26-CreER<\/jats:italic>\n                    and\n                    <jats:italic>Vav-CreER<\/jats:italic>\n                    ) and will make these exciting new tools for studies on cell death and cancer available.\n                  <\/jats:p>","DOI":"10.1038\/cddis.2014.409","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T09:03:45Z","timestamp":1412845425000},"page":"e1446-e1446","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Impact of conditional deletion of the pro-apoptotic BCL-2 family member BIM in mice"],"prefix":"10.1038","volume":"5","author":[{"given":"M J","family":"Herold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Stuchbery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"M\u00e9rino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Willson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Strasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Hildeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Bouillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,10,9]]},"reference":[{"key":"BFcddis2014409_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrm3722","volume":"15","author":"PE Czabotar","year":"2013","unstructured":"Czabotar PE, Lessene G, Strasser A, Adams JM . Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 2013; 15: 49\u201363.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcddis2014409_CR2","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrm2308","volume":"9","author":"RJ Youle","year":"2008","unstructured":"Youle RJ, Strasser A . The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9: 47\u201359.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcddis2014409_CR3","doi-asserted-by":"publisher","first-page":"S128","DOI":"10.1038\/onc.2009.50","volume":"27","author":"M Giam","year":"2008","unstructured":"Giam M, Huang DC, Bouillet P . BH3-only proteins and their roles in programmed cell death. 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