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Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk

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Abstract

THE tyrosine kinase Syk (relative molecular mass 72,000), which is widely expressed in haematopoietic cells, becomes associated with and activated by engagement of the B-cell antigen receptor1,2. Furthermore, it has been implicated in signalling through the receptors for interleukin-2 (IL-2)3, granulocyte colony-stimulating factor (G-CSF)4 and Fc5, the T cell receptor, as well as through receptors for several platelet agonists7. A homologous kinase, ZAP-70, is crucial in signalling through the T-cell receptor and in T-cell development8,9. Using homologous recombination in embryonic stem cells, we created mice null for the syk gene which showed petechiae in utero and died shortly after birth. Irradiated mice reconstituted with Syk-deficient fetal liver showed a block in B-cell development at the pro-B to pre-B cell transition, consistent with a key role for Syk in pre-B-cell receptor signalling. Despite the production of small numbers of immature B cells, Syk-deficient radiation chimaeras failed to accumulate mature B cells, indicating a possible role for this protein in the production or maintenance of mature B cells. In addition, whereas the development of αβ T cells proceeded normally, Syk-deficient mice showed impaired development of thymocytes using the Vγ3 variable region gene (Vγ3+ thymocytes). Finally, we show that Syk is not required for signalling through the IL-2 and G-CSF receptors.

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Author notes

  1. Michael T. Furlong and Robert L. Geahlen: Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Indiana 47907, USA

Authors and Affiliations

  1. National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Martin Turner, P. Joseph Mee, Patrick S. Costello, Owen Williams, Abigail A. Price, Linda P. Duddy, Michael T. Furlong, Robert L. Geahlen & Victor L. J. Tybulewicz

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  1. Martin Turner
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  2. P. Joseph Mee
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  3. Patrick S. Costello
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  4. Owen Williams
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  5. Abigail A. Price
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  6. Linda P. Duddy
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  7. Michael T. Furlong
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  8. Robert L. Geahlen
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  9. Victor L. J. Tybulewicz
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Turner, M., Joseph Mee, P., Costello, P. et al. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 378, 298–302 (1995). https://doi.org/10.1038/378298a0

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