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Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2

The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor γ chain (γ(c)) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferat...

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Autores principales: Rodewald, Hans-Reimer, Waskow, Claudia, Haller, Corinne
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193302/
https://www.ncbi.nlm.nih.gov/pubmed/11413198
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author Rodewald, Hans-Reimer
Waskow, Claudia
Haller, Corinne
author_facet Rodewald, Hans-Reimer
Waskow, Claudia
Haller, Corinne
author_sort Rodewald, Hans-Reimer
collection PubMed
description The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor γ chain (γ(c)) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferation, survival, or differentiation, but the contribution of each receptor to distinct intracellular signaling cascades is only poorly defined. Here, we have examined whether enforced expression of Bcl-2 can rescue thymocyte development in c-kit and γ(c) single or double mutant mice. A bcl-2 transgene (Eμ-bcl-2-25; expressed in the T cell lineage) was introduced into (a) c-kit and γ(c) wild-type (c-kit(+)γ(c) (+)bcl(+)), (b) c-kit–deficient (c-kit(−)γ(c) (+)bcl(+)), (c) γ(c)-deficient (c-kit(+)γ(c) (−)bcl(+)), or (d) c-kit and γ(c) double-deficient mice (c-kit(−)γ(c) (−)bcl(+)). The bcl-2 transgene was functionally active in wild-type and c-kit or γ(c) single mutants, as it promoted survival of ex vivo isolated thymocytes, including pro-T cells. In vivo, however, transgenic Bcl-2 did not release T cell precursors from their phenotypic block and failed to increase progenitor or total thymocyte cellularity in c-kit or γ(c) single or double mutants. These data argue strongly against a role for Bcl-2 as a key mediator in signaling pathways linked to cytokine and growth factor receptors driving early thymocyte development.
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spelling pubmed-21933022008-04-14 Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2 Rodewald, Hans-Reimer Waskow, Claudia Haller, Corinne J Exp Med Brief Definitive Report The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor γ chain (γ(c)) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferation, survival, or differentiation, but the contribution of each receptor to distinct intracellular signaling cascades is only poorly defined. Here, we have examined whether enforced expression of Bcl-2 can rescue thymocyte development in c-kit and γ(c) single or double mutant mice. A bcl-2 transgene (Eμ-bcl-2-25; expressed in the T cell lineage) was introduced into (a) c-kit and γ(c) wild-type (c-kit(+)γ(c) (+)bcl(+)), (b) c-kit–deficient (c-kit(−)γ(c) (+)bcl(+)), (c) γ(c)-deficient (c-kit(+)γ(c) (−)bcl(+)), or (d) c-kit and γ(c) double-deficient mice (c-kit(−)γ(c) (−)bcl(+)). The bcl-2 transgene was functionally active in wild-type and c-kit or γ(c) single mutants, as it promoted survival of ex vivo isolated thymocytes, including pro-T cells. In vivo, however, transgenic Bcl-2 did not release T cell precursors from their phenotypic block and failed to increase progenitor or total thymocyte cellularity in c-kit or γ(c) single or double mutants. These data argue strongly against a role for Bcl-2 as a key mediator in signaling pathways linked to cytokine and growth factor receptors driving early thymocyte development. The Rockefeller University Press 2001-06-18 /pmc/articles/PMC2193302/ /pubmed/11413198 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Rodewald, Hans-Reimer
Waskow, Claudia
Haller, Corinne
Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
title Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
title_full Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
title_fullStr Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
title_full_unstemmed Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
title_short Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
title_sort essential requirement for c-kit and common γ chain in thymocyte development cannot be overruled by enforced expression of bcl-2
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193302/
https://www.ncbi.nlm.nih.gov/pubmed/11413198
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