title: Regulator of G-protein signaling 18 controls both platelet generation and function.
abstract: RGS18 is a myeloerythroid lineage-specific regulator of G-protein signaling, highly expressed in megakaryocytes (MKs) and platelets. In the present study, we describe the first generation of a RGS18 knockout mouse model (RGS18-/-). Interesting phenotypic differences between RGS18-/- and wild-type (WT) mice were identified, and show that RGS18 plays a significant role in both platelet generation and function. RGS18 deficiency produced a gain of function phenotype in platelets. In resting platelets, the level of CD62P expression was increased in RGS18-/- mice. This increase correlated with a higher level of plasmatic serotonin concentration. RGS18-/- platelets displayed a higher sensitivity to activation in vitro. RGS18 deficiency markedly increased thrombus formation in vivo. In addition, RGS18-/- mice presented a mild thrombocytopenia, accompanied with a marked deficit in MK number in the bone marrow. Analysis of MK maturation in vitro and in vivo revealed a defective megakaryopoiesis in RGS18-/- mice, with a lower bone marrow content of only the most committed MK precursors. Finally, RGS18 deficiency was correlated to a defect of platelet recovery in vivo under acute conditions of thrombocytopenia. Thus, we highlight a role for RGS18 in platelet generation and function, and provide additional insights into the physiology of RGS18.
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delesque-Touchard
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pendaries
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Volle-Challier
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Millet
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Salel
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hervé
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Pflieger
authors.affiliation: SCP Biologics, Sanofi, Vitry-Sur-Seine, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Berthou-Soulie
authors.affiliation: SCP Biologics, Sanofi, Vitry-Sur-Seine, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Prades
authors.affiliation: Department of Scientific Operations PhenoPro, Mouse Clinical Institute (MCI), Strasbourg, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Sorg
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Savi
authors.affiliation: Early to Candidate (E2C), Sanofi, Toulouse, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Bono
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001772:Blood Cell Count; D005434:Flow Cytometry; D008533:Megakaryocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010802:Phylogeny; D015539:Platelet Activation / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism*; D012701:Serotonin / Q000097:blood; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013927:Thrombosis / Q000378:metabolism
chemical_list: D020710:RGS Proteins; C422991:Rgs18 protein, mouse; D012701:Serotonin