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

327 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

Access to Document

10.1016/S0092-8674(00)81422-1

Cite this

@article{ba8ae1fe225a446e84b8e660648a8f3e,

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",

month = jul,

day = "24",

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

language = "English (US)",

volume = "94",

pages = "229--238",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "2",

}

TY - JOUR

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.

UR - https://www.scopus.com/pages/publications/0032563256

UR - https://www.scopus.com/inward/citedby.url?scp=0032563256&partnerID=8YFLogxK

U2 - 10.1016/S0092-8674(00)81422-1

DO - 10.1016/S0092-8674(00)81422-1

M3 - Article

C2 - 9695951

AN - SCOPUS:0032563256

SN - 0092-8674

VL - 94

SP - 229

EP - 238

JO - Cell

JF - Cell

IS - 2

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this