The role of previously uncharacterized RNA binding proteins in hematopoiesis

Abstract

The crucial checkpoints that determine T-cell fate along with various differentiation pathways have been genetically defined. Still there are many uncharacterized genes whose roles in thymus and T cell development have yet to be established. One such example is Thymocyte specific cAMP-regulated phosphoprotein (thymocyte Arpp21 or Tarpp). Although TARPP protein is highly expressed in immature T cells and is down-regulated immediately after T-cell receptor (TCR) gene rearrangements, Tarpp KO mice did not have any apparent immunological phenotype. We hypothesized that two other proteins sharing high homology and RNA-binding domains with TARPP, R3h-domain containing protein 1 and 2 (R3HDM1 and R3HDM2) are able to compensate its function in vivo. Through generation of R3hdm1 and R3hdm2 KO mice, we intended to characterize role of these two RNA-binding proteins in murine hematopoiesis. R3hdm1, R3hdm2 and newly derived Tarpp KO (-/-) mice were viable but surprisingly did not have any immunological phenotype. R3hdm1 KO mice showed a reproductive phenotype with reduced litter size and disrupted internal testis architecture. This report provides more information about structure and genetic organization of these genes. Phenotypic analysis of double or triple KO mice will shed light on the function of these R3H domain containing proteins in T-cell physiology.