Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76

Vadim Pivniouk; Erdyni Tsitsikov; Paul Swinton; Gary Rathbun; Frederick W. Alt; Raif S. Geha

doi:10.1016/S0092-8674(00)81422-1

Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76

Vadim Pivniouk, Erdyni Tsitsikov, Paul Swinton, Gary Rathbun, Frederick W. Alt, Raif S. Geha

Research output: Contribution to journal › Article › peer-review

326 Scopus citations

Abstract

The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation, SLP-76- deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4⁺8⁺ thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCRβ locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.

Original language	English (US)
Pages (from-to)	229-238
Number of pages	10
Journal	Cell
Volume	94
Issue number	2
DOIs	https://doi.org/10.1016/S0092-8674(00)81422-1
State	Published - Jul 24 1998
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(00)81422-1

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title = "Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76",

abstract = "The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation, SLP-76- deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4+8+ thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCRβ locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.",

author = "Vadim Pivniouk and Erdyni Tsitsikov and Paul Swinton and Gary Rathbun and Alt, {Frederick W.} and Geha, {Raif S.}",

note = "Funding Information: This work was supported by NIH grant AI-35714; by grants from Baxter Healthcare, Alpha Therapeutics, and Olsten Corporations to R. S. G.; and a grant from the Howard Hughes Medical Institutes (F. W. A.).",

year = "1998",

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doi = "10.1016/S0092-8674(00)81422-1",

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T1 - Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76

AU - Pivniouk, Vadim

AU - Tsitsikov, Erdyni

AU - Swinton, Paul

AU - Rathbun, Gary

AU - Alt, Frederick W.

AU - Geha, Raif S.

N1 - Funding Information: This work was supported by NIH grant AI-35714; by grants from Baxter Healthcare, Alpha Therapeutics, and Olsten Corporations to R. S. G.; and a grant from the Howard Hughes Medical Institutes (F. W. A.).

PY - 1998/7/24

Y1 - 1998/7/24

N2 - The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation, SLP-76- deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4+8+ thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCRβ locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.

AB - The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation, SLP-76- deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4+8+ thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCRβ locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.

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JO - Cell

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Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76

Abstract

ASJC Scopus subject areas

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