{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:31:58Z","timestamp":1791325918055,"version":"4.3.1"},"reference-count":47,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[1994,10,1]],"date-time":"1994-10-01T00:00:00Z","timestamp":780969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Most examples of cell death in animals are controlled by a genetic program that is activated within the dying cell. The apoptotic process is further regulated by a set of genes that act as repressors of cell death. Of these, bcl-2 is expressed in a variety of embryonic and postnatal tissues which suggests a critical role for bcl-2 in organogenesis and tissue homeostasis. Surprisingly, mutant mice with targeted disruption of bcl-2 appear normal at birth and complete maturation of lymphoid tissues before succumbing to fulminant lymphopenia and polycystic renal disease by 2-5 weeks of age. This suggests that there may be genes other than bcl-2 that can regulate apoptosis during development. To begin to investigate this possibility, we have cloned and characterized the murine bcl-x gene, whose human counterpart displays striking homology to bcl-2. The predicted murine bcl-xL gene product exhibits a high level of amino acid identity (97%) to its human counterpart. Just like Bcl-2, the murine bcl-xL gene product can act as a dominant inhibitor of cell death upon growth factor withdrawal. In addition, the bulk of the bcl-xL product localizes to the periphery of mitochondria as assessed by a bcl-xL-tag expression system, suggesting that both Bcl-2 and Bcl-xL proteins prevent cell death by a similar mechanism. bcl-xL is the most abundant bcl-x mRNA species expressed in embryonic and adult tissues. The levels of bcl-xL mRNA appear higher than those of bcl-2 during embryonal development and in several adult organs including bone marrow, brain, kidney and thymus. In addition to bcl-xL, we have identified another form of bcl-x mRNA, bcl-x\u03b2, that results from an unspliced bcl-x transcript. bcl-x\u03b2 mRNA is expressed in various embryonic and postnatal tissues. Surprisingly, the expression of bcl-xS (a negative regulator of programmed cell death) was undetectable by a sensitive S1-nuclease assay and polymerase chain reaction analysis of mouse tissues. Based on its tissue and developmental patterns of expression, it appears that bcl-x may play an important role in the regulation of cell death during development and tissue homeostasis.<\/jats:p>","DOI":"10.1242\/dev.120.10.3033","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T21:33:27Z","timestamp":1619386407000},"page":"3033-3042","source":"Crossref","is-referenced-by-count":338,"title":["<i>bcl-xLx<\/i>\n                    is the major\n                    <i>bcl-x<\/i>\n                    mRNA form expressed during murine development and its product localizes to mitochondria"],"prefix":"10.1242","volume":"120","author":[{"given":"Maribel","family":"Gonz\u00e1lez-Garc\u00eda","sequence":"first","affiliation":[{"name":"University of Michigan Medical School 1 Department of Pathology , , Ann Arbor, Michigan 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"P\u00e9rez-Ballestero","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School 1 Department of Pathology , , Ann Arbor, Michigan 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Ding","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School 1 Department of Pathology , , Ann Arbor, Michigan 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Duan","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School 1 Department of Pathology , , Ann Arbor, Michigan 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence H.","family":"Boise","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 2 , Departments of Medicine, Molecular Genetics and Cell Biology , , C hicago, Illinois 60637, USA"},{"name":"University of Chicago 2 , Departments of Medicine, Molecular Genetics and Cell Biology , , C hicago, Illinois 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig B.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 2 , Departments of Medicine, Molecular Genetics and Cell Biology , , C hicago, Illinois 60637, USA"},{"name":"University of Chicago 2 , Departments of Medicine, Molecular Genetics and Cell Biology , , C hicago, Illinois 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School 1 Department of Pathology , , Ann Arbor, Michigan 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1994,10,1]]},"reference":[{"key":"2024121723470247400_DEVELOP_120_10_3033C1","doi-asserted-by":"publisher","first-page":"6511","DOI":"10.1016\/S0021-9258(18)53280-4","article-title":"Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoproteinproduction","volume":"268","author":"Baffy","year":"1993","journal-title":"J. Biol. Chem"},{"key":"2024121723470247400_DEVELOP_120_10_3033C2","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1210\/mend-5-5-637","article-title":"Genes newly identified as regulated by glucocorticoids in murine thymocytes","volume":"5","author":"Baughman","year":"1991","journal-title":"Molec. Endocrinol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C3","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/0092-8674(93)90508-N","article-title":"bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death","volume":"74","author":"Boise","year":"1993","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C4","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/0092-8674(93)90115-7","article-title":"The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye","volume":"72","author":"Bonini","year":"1993","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C5","first-page":"701","article-title":"The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye","volume":"9","author":"Chen-Levy","year":"1989","journal-title":"Mol. Cell. Biol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C6","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1038\/362849a0","article-title":"Thymocyte apoptosis induced by p53-dependent and independent pathways","volume":"362","author":"Clarke","year":"1993","journal-title":"Nature"},{"key":"2024121723470247400_DEVELOP_120_10_3033C7","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0065-2776(08)60822-6","article-title":"Programmed cell death in the immune system","volume":"50","author":"Cohen","year":"1991","journal-title":"Adv. Immunol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C8","doi-asserted-by":"publisher","first-page":"38","DOI":"10.4049\/jimmunol.132.1.38","article-title":"Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death","volume":"32","author":"Cohen","year":"1984","journal-title":"J. Immunol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C9","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1002\/j.1460-2075.1993.tb05799.x","article-title":"Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells","volume":"12","author":"Cuende","year":"1993","journal-title":"EMBO J"},{"key":"2024121723470247400_DEVELOP_120_10_3033C10","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1021\/bi00591a005","article-title":"Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease","volume":"18","author":"Chirgwin","year":"1979","journal-title":"Biochemistry"},{"key":"2024121723470247400_DEVELOP_120_10_3033C11","doi-asserted-by":"publisher","first-page":"4187","DOI":"10.1093\/nar\/20.16.4187","article-title":"Isolation and characterization of the chicken bcl-2 gene: expression in a variety of tissues including lymphoid and neuronal organs in adult and embryo","volume":"20","author":"Eguchi","year":"1992","journal-title":"Nucl. Acids Res"},{"key":"2024121723470247400_DEVELOP_120_10_3033C12","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/0092-8674(86)90004-8","article-title":"Genetic control of programmed cell death in the nematode C. elegans","volume":"44","author":"Ellis","year":"1986","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C13","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1146\/annurev.cb.07.110191.003311","article-title":"Mechanisms and functions of cell death","volume":"7","author":"Ellis","year":"1991","journal-title":"Annu Rev. Cell Biol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C14","doi-asserted-by":"publisher","first-page":"5649","DOI":"10.1073\/pnas.85.15.5649","article-title":"Expression of membrane interleukin 1 by fibroblasts transfected with murine pro-interleukin 1 alpha cDNA","volume":"85","author":"Fuhlbrigge","year":"1988","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2024121723470247400_DEVELOP_120_10_3033C15","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1126\/science.1411528","article-title":"Prevention of programmed cell death of sympathetic neurons by the bcl-2 protooncogene","volume":"258","author":"Garc\u00eda","year":"1992","journal-title":"Science"},{"key":"2024121723470247400_DEVELOP_120_10_3033C16","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1469-185X.1951.tb00774.x","article-title":"Cell deaths in normal vertebrate ontogeny","volume":"26","author":"Glucksmann","year":"1951","journal-title":"Biol . Rev. Cambridge Philos. Soc"},{"key":"2024121723470247400_DEVELOP_120_10_3033C17","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/356494a0","article-title":"Caenorhabditis elegans gene ced-9 protects cells from programmed cell death","volume":"356","author":"Hengartner","year":"1992","journal-title":"Nature"},{"key":"2024121723470247400_DEVELOP_120_10_3033C18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-94-011-6921-9_3","volume-title":"Cell Death in Biology and Pathology","author":"Hinchliffe","year":"1981"},{"key":"2024121723470247400_DEVELOP_120_10_3033C19","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/348334a0","article-title":"Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death","volume":"348","author":"Hockenbery","year":"1990","journal-title":"Nature"},{"key":"2024121723470247400_DEVELOP_120_10_3033C20","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/0092-8674(93)80066-N","article-title":"Bcl-2 functions in an antioxidant pathway to prevent apoptosis","volume":"75","author":"Hockenbery","year":"1993","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C21","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1038\/nbt1088-1204","article-title":"A short polypeptide marker sequence useful for recombinant protein identification and purification","volume":"6","author":"Hopp","year":"1988","journal-title":"Bio\/Technology"},{"key":"2024121723470247400_DEVELOP_120_10_3033C22","doi-asserted-by":"publisher","first-page":"3887","DOI":"10.1002\/j.1460-2075.1992.tb05481.x","article-title":"Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death","volume":"11","author":"Ishida","year":"1992","journal-title":"EMBO J"},{"key":"2024121723470247400_DEVELOP_120_10_3033C23","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/361365a0","article-title":"Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA","volume":"361","author":"Jacobson","year":"1993","journal-title":"Nature"},{"key":"2024121723470247400_DEVELOP_120_10_3033C24","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1126\/science.8235659","article-title":"Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species","volume":"262","author":"Kane","year":"1993","journal-title":"Science"},{"key":"2024121723470247400_DEVELOP_120_10_3033C25","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/0076-6879(91)94038-E","article-title":"Epitope tagging and protein surveillance","volume":"194","author":"Kolodziej","year":"1991","journal-title":"Methods Enzymol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C26","doi-asserted-by":"publisher","first-page":"8125","DOI":"10.1093\/nar\/15.20.8125","article-title":"An analysis of 5\u2032-noncoding sequences from 699 vertebrate messenger RNAs","volume":"15","author":"Kozak","year":"1987","journal-title":"Nucl. Acids Res"},{"key":"2024121723470247400_DEVELOP_120_10_3033C27","first-page":"4701","article-title":"Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes","volume":"53","author":"Krajewski","year":"1993","journal-title":"Cancer Res"},{"key":"2024121723470247400_DEVELOP_120_10_3033C28","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/362847a0","article-title":"p53 is required for radiation-induced apoptosis in mouse thymocytes","volume":"362","author":"Lowe","year":"1993","journal-title":"Nature"},{"key":"2024121723470247400_DEVELOP_120_10_3033C29","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1083\/jcb.106.3.829","article-title":"Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation","volume":"106","author":"Martin","year":"1988","journal-title":"J. Cell Biol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C30","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/1523-1747.ep12478519","article-title":"Programmed cell death in terminally differentiating keratinocytes: role of endogenous endonuclease","volume":"97","author":"McCall","year":"1991","journal-title":"J. Invest. Dermatol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C31","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1242\/dev.120.2.301","article-title":"bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS","volume":"120","author":"Merry","year":"1994","journal-title":"Development"},{"key":"2024121723470247400_DEVELOP_120_10_3033C32","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/0092-8674(93)90486-A","article-title":"Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3","volume":"75","author":"Miura","year":"1993","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C33","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1177\/40.12.1453000","article-title":"Ultrastructural localization of bcl-2 protein","volume":"40","author":"Monaghan","year":"1992","journal-title":"J. Histochem. Cytochem"},{"key":"2024121723470247400_DEVELOP_120_10_3033C34","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1126\/science.8372353","article-title":"Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice","volume":"261","author":"Nakayama","year":"1993","journal-title":"Science"},{"key":"2024121723470247400_DEVELOP_120_10_3033C35","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/0092-8674(87)90448-X","article-title":"Molecular analysis of mbcl-2: structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma","volume":"49","author":"Negrini","year":"1987","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C36","doi-asserted-by":"publisher","first-page":"25265","DOI":"10.1016\/S0021-9258(19)74386-5","article-title":"Targeting of Bcl-2 to the mitochondrial outer membrane by a COOH-terminal signal anchor sequence","volume":"268","author":"Nguyen","year":"1993","journal-title":"J. Biol. Chem"},{"key":"2024121723470247400_DEVELOP_120_10_3033C37","doi-asserted-by":"publisher","first-page":"3602","DOI":"10.4049\/jimmunol.144.9.3602","article-title":"Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines","volume":"144","author":"N\u00fa\u00f1ez","year":"1990","journal-title":"J. Immunol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C38","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.ne.14.030191.002321","article-title":"Cell death during development of the nervous system","volume":"14","author":"Oppenheim","year":"1991","journal-title":"Annu. Rev. Neurosci"},{"key":"2024121723470247400_DEVELOP_120_10_3033C39","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1128\/MCB.11.8.4177","article-title":"Identification of mRNAs associated with programmed cell death in immature thymocytes","volume":"11","author":"Owens","year":"1991","journal-title":"Mol. Cell. Biol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C40","first-page":"711","article-title":"Cell cycle analysis of p53-induced cell death in murine erythroleukemia cells","volume":"13","author":"Ryan","year":"1993","journal-title":"Mol. Cell. Biol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C41","doi-asserted-by":"publisher","first-page":"5214","DOI":"10.1073\/pnas.83.14.5214","article-title":"Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma","volume":"83","author":"Tsujimoto","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024121723470247400_DEVELOP_120_10_3033C42","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/335440a0","article-title":"Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells","volume":"335","author":"Vaux","year":"1988","journal-title":"Nature"},{"key":"2024121723470247400_DEVELOP_120_10_3033C43","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0092-8674(93)80065-M","article-title":"Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair","volume":"75","author":"Veis","year":"1993","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C44","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/0092-8674(91)90002-G","article-title":"Programmed cell death: apoptosis and oncogenesis","volume":"65","author":"Williams","year":"1991","journal-title":"Cell"},{"key":"2024121723470247400_DEVELOP_120_10_3033C45","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/352345a0","article-title":"Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6","volume":"352","author":"Yonish-Rouach","year":"1991","journal-title":"Nature"},{"key":"2024121723470247400_DEVELOP_120_10_3033C46","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0012-1606(90)90174-H","article-title":"The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death","volume":"138","author":"Yuan","year":"1990","journal-title":"Dev. Biol"},{"key":"2024121723470247400_DEVELOP_120_10_3033C47","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/0092-8674(93)90485-9","article-title":"The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme","volume":"75","author":"Yuan","year":"1993","journal-title":"Cell"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/120\/10\/3033\/3594151\/develop_120_10_3033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/120\/10\/3033\/3594151\/develop_120_10_3033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T18:47:25Z","timestamp":1734461245000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/120\/10\/3033\/38172\/bcl-xLx-is-the-major-bcl-x-mRNA-form-expressed"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,10,1]]},"references-count":47,"journal-issue":{"issue":"10","published-print":{"date-parts":[[1994,10,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.120.10.3033","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,10,1]]}}}