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Article: Brca1 required for T cell lineage development but not TCR loci rearrangement

TitleBrca1 required for T cell lineage development but not TCR loci rearrangement
Authors
Issue Date2000
Citation
Nature Immunology, 2000, v. 1, n. 1, p. 77-82 How to Cite?
AbstractBrca1 (breast cancer1, early onset) deficiency results in early embryonic lethality. As Brca1 is highly expressed in the T cell lineage, a T cell-specific disruption of Brca1 was generated to assess the role of Brca1 in relation to T lymphocyte development. We found that thymocyte development in Brca1-/- mice was impaired not as a result of V(D)J T cell receptor (TCR) recombination but because thymocytes had increased expression of tumor protein p53. Chromosomal damage accumulation and abnormal cell death were observed in mutant cells. We found that cell death inhibitor Bcl-2 overexpression, or p53-/- backgrounds, completely restored survival and development of Brca1-/- thymocytes; peripheral T cell numbers were not totally restored in Brca1-/- p53-/- mice; and that a mutant background for p21 (cyclin-dependent kinase inhibitor IA) did not restore Brca1-/- thymocyte development, but partially restored peripheral T cell development. Thus, the outcome of Brca1 deficiency was dependent on cellular context, with the major defects being increased apoptosis in thymocytes, and defective proliferation in peripheral T cells.
Persistent Identifierhttp://hdl.handle.net/10722/291939
ISSN
2023 Impact Factor: 27.7
2023 SCImago Journal Rankings: 11.274
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMak, Tak W.-
dc.contributor.authorHakem, Anne-
dc.contributor.authorMcPherson, J. Peter-
dc.contributor.authorShehabeldin, Amro-
dc.contributor.authorZablocki, Elzbieta-
dc.contributor.authorMigon, Eva-
dc.contributor.authorDuncan, Gordon S.-
dc.contributor.authorBouchard, Denis-
dc.contributor.authorWakeham, Andrew-
dc.contributor.authorCheung, Alison-
dc.contributor.authorKaraskova, Jana-
dc.contributor.authorSarosi, Ildiko-
dc.contributor.authorSquire, Jeremy-
dc.contributor.authorMarth, Jamey-
dc.contributor.authorHakem, Razqallah-
dc.date.accessioned2020-11-17T14:55:25Z-
dc.date.available2020-11-17T14:55:25Z-
dc.date.issued2000-
dc.identifier.citationNature Immunology, 2000, v. 1, n. 1, p. 77-82-
dc.identifier.issn1529-2908-
dc.identifier.urihttp://hdl.handle.net/10722/291939-
dc.description.abstractBrca1 (breast cancer1, early onset) deficiency results in early embryonic lethality. As Brca1 is highly expressed in the T cell lineage, a T cell-specific disruption of Brca1 was generated to assess the role of Brca1 in relation to T lymphocyte development. We found that thymocyte development in Brca1-/- mice was impaired not as a result of V(D)J T cell receptor (TCR) recombination but because thymocytes had increased expression of tumor protein p53. Chromosomal damage accumulation and abnormal cell death were observed in mutant cells. We found that cell death inhibitor Bcl-2 overexpression, or p53-/- backgrounds, completely restored survival and development of Brca1-/- thymocytes; peripheral T cell numbers were not totally restored in Brca1-/- p53-/- mice; and that a mutant background for p21 (cyclin-dependent kinase inhibitor IA) did not restore Brca1-/- thymocyte development, but partially restored peripheral T cell development. Thus, the outcome of Brca1 deficiency was dependent on cellular context, with the major defects being increased apoptosis in thymocytes, and defective proliferation in peripheral T cells.-
dc.languageeng-
dc.relation.ispartofNature Immunology-
dc.titleBrca1 required for T cell lineage development but not TCR loci rearrangement-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/76950-
dc.identifier.pmid10881179-
dc.identifier.scopuseid_2-s2.0-7444231187-
dc.identifier.volume1-
dc.identifier.issue1-
dc.identifier.spage77-
dc.identifier.epage82-
dc.identifier.isiWOS:000089814800018-
dc.identifier.issnl1529-2908-

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