Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal homeostasis and survival.
[EN] Sos1 and Sos2 are ubiquitously expressed, universal Ras guanine nucleotide exchange factors (Ras-GEFs) acting in multiple signal transduction pathways activated by upstream cellular kinases. The embryonic lethality of Sos1 null mutants has hampered ascertaining the specific in vivo contribution...
| Authors: | , , , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2013 |
| Country: | España |
| Institution: | Universidad de Salamanca (USAL) |
| Repository: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/169118 |
| Online Access: | http://hdl.handle.net/10366/169118 |
| Access Level: | Embargoed access |
| Keyword: | SOS1 Protein Bone marrow transplant B-Lymphocytes T-Lymphocytes Lymphopoiesis Homeostasis Animals Son of Sevenless Proteins Lymphoid Progenitor Cells Cell Count Mice 2412 Inmunología 2415 Biología Molecular animales linfocitos B recuento de células ratones homeostasis células progenitoras de linfocitos proteína SOS1 linfocitos T proteínas SOS linfopoyesis |
| Summary: | [EN] Sos1 and Sos2 are ubiquitously expressed, universal Ras guanine nucleotide exchange factors (Ras-GEFs) acting in multiple signal transduction pathways activated by upstream cellular kinases. The embryonic lethality of Sos1 null mutants has hampered ascertaining the specific in vivo contributions of Sos1 and Sos2 to processes controlling adult organism survival or development of hematopoietic and nonhematopoietic organs, tissues, and cell lineages. Here, we generated a tamoxifen-inducible Sos1-null mouse strain allowing analysis of the combined disruption of Sos1 and Sos2 (Sos1/2) during adulthood. Sos1/2 double-knockout (DKO) animals died precipitously, whereas individual Sos1 and Sos2 knockout (KO) mice were perfectly viable. A reduced percentage of total bone marrow precursors occurred in single-KO animals, but a dramatic depletion of B-cell progenitors was specifically detected in Sos1/2 DKO mice. We also confirmed a dominant role of Sos1 over Sos2 in early thymocyte maturation, with almost complete thymus disappearance and dramatically higher reduction of absolute thymocyte counts in Sos1/2 DKO animals. Absolute counts of mature B and T cells in spleen and peripheral blood were unchanged in single-KO mutants, while significantly reduced in Sos1/2 DKO mice. Our data demonstrate functional redundancy between Sos1 and Sos2 for homeostasis and survival of the full organism and for development and maturation of T and B lymphocytes. |
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