Regulator of G-protein signaling 18 controls both platelet generation and function

PLoS One. 2014 Nov 18;9(11):e113215. doi: 10.1371/journal.pone.0113215. eCollection 2014.


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.

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Cell Count
  • Flow Cytometry
  • Megakaryocytes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phylogeny
  • Platelet Activation / genetics
  • Platelet Activation / physiology*
  • Promoter Regions, Genetic / genetics
  • RGS Proteins / genetics*
  • RGS Proteins / metabolism*
  • Serotonin / blood
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Thrombosis / metabolism


  • RGS Proteins
  • Rgs18 protein, mouse
  • Serotonin

Grants and funding

In addition, the authors received no specific funding for this work. Sanofi provided support in the form of salaries for authors ND-T, C. Pendaries, CV-C, LM, VS, CH, A-MP, LB-S, C. Prades, J-MH, PS and FB. Sanofi had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.