title: Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal homeostasis and survival.
abstract: 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.
authors.affiliation: Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca) Lab 1, Salamanca, Spain.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Baltanás
authors.forename: Martín
authors.initials: M
authors.lastname: Pérez-Andrés
authors.forename: Alicia
authors.initials: A
authors.lastname: Ginel-Picardo
authors.forename: David
authors.initials: D
authors.lastname: Diaz
authors.forename: David
authors.initials: D
authors.lastname: Jimeno
authors.forename: Pilar
authors.initials: P
authors.lastname: Liceras-Boillos
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kortum
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Samelson
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Eugenio
authors.initials: E
authors.lastname: Santos
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D005260:Female; D006706:Homeostasis; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D038041:Lymphopoiesis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020837:SOS1 Protein / Q000235:genetics / Q000378:metabolism*; D020664:Son of Sevenless Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D020837:SOS1 Protein; D020664:Son of Sevenless Proteins; C116864:Sos2 protein, mouse
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