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Updated: Jul 9, 2026
Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
Published on: April 3, 2011
Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76
V Pivniouk1, E Tsitsikov, P Swinton
1Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
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 TCRbeta 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.
Insights
Signaling lymphocytic protein 76 (SLP-76) is crucial for T cell development. SLP-76-deficient mice show blocked thymocyte development and lack peripheral T cells, indicating its essential role in pre-TCR signaling.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Signaling lymphocytic protein 76 (SLP-76) is an adaptor protein found in T lymphocytes and myeloid cells.
- SLP-76 acts as a substrate for ZAP-70 and Syk tyrosine kinases, key players in immune cell signaling.
Purpose of the Study:
- To investigate the role of SLP-76 in T cell development and activation.
- To characterize the consequences of a SLP-76 null mutation in mice.
Main Methods:
- Generation of SLP-76 null mutant mice using homologous recombination in embryonic stem cells.
- Analysis of lymphoid cell populations and thymic development in SLP-76-deficient mice.
- Assessment of T cell receptor beta (TCRbeta) V-D-J rearrangement and B cell development.
Main Results:
- SLP-76-deficient mice displayed significant hemorrhaging and reduced viability.
- A severe block in thymic development was observed, with an absence of double-positive CD4+8+ thymocytes and peripheral T cells.
- In vivo treatment with anti-CD3 failed to rescue the developmental block.
- TCRbeta V-D-J rearrangement and B cell development remained unaffected.
Conclusions:
- SLP-76 is essential for the pre-TCR signaling pathway that drives the development and expansion of double-positive thymocytes.
- The adaptor protein SLP-76 is indispensable for normal T cell maturation and survival.
