Immunological Function in Mice Lacking the Rac-Related GTPase RhoG

Abstract

RhoG is a low-molecular-weight GTPase highly expressed in lymphocytes that activates gene transcription and promotes cytoskeletal reorganization in vitro. To study the in vivo function of RhoG, we generated mice homozygous for a targeted disruption of the RhoG gene. Despite the absence of RhoG, the development of B and T lymphocytes was unaffected. However, there was an increase in the level of serum immunoglobulin G1 (IgG1) and IgG2b as well as a mild increase of the humoral immune response to thymus-dependent antigens. In addition, B-and T-cell proliferation in response to antigen receptor cross-linking was slightly increased. Although RhoG deficiency produces a mild phenotype, our experiments suggest that RhoG may contribute to the negative regulation of immune responses. The lack of a strong phenotype could indicate a functional redundancy of RhoG with other Rac proteins in lymphocytes.

RhoG Regulates the Neutrophil NADPH Oxidase

“…Ϫ/Ϫ mice on a mixed C57BL/6, 129/Sv background were obtained by targeted disruption of the RhoG gene as previously described (20). Wildtype (wt) controls were mixed C57BL/6, 129/Sv derived from wt littermates bred in parallel.…”

“…Reported functional consequences of RhoG activation include formation of dorsal ruffles (16), neurite outgrowth from PC12 cells (17), stimulation of macropinocytosis (16), and engulfment of apoptotic cells (18). RhoG has additionally been implicated in lymphocyte signaling, transcriptional regulation, and cytoskeletal rearrangements (19), but lymphocytes derived from a RhoG Ϫ/Ϫ mouse demonstrated only minor functional and signaling abnormalities (20).…”

Role of chimaerins, a group of Rac-specific GTPase activating proteins, in T-cell receptor signaling

“…Although much less characterized, there is also information regarding the participation of RhoG in the regulation of the cytoskeleton and NF-AT activities in T-cells [12]. However, rhoG deficient mice show no major alterations in Tcell biology [13]. Rac proteins also play roles at the level of antigen presenting cells, since the combined deletion of rac1 and rac2 genes impairs the antigen-presenting activity of dendritic cells in mice [10,14].…”

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

“…RhoG Ϫ/Ϫ mice have elevated levels of IgG1 and IgG2b antibodies. There is a mild hyper-reactivity defect in RhoGdeficient B2 cells or T cells (18). RhoG is thought to induce actin rearrangements and membrane protrusion by Rac activation through the ELMO-DOCK180 pathway.…”

“…RhoA, Rac, and Cdc42 have been shown to control the assembly of focal adhesion complexes associated with actin-myosin filaments, lamellipodia, and filopodia, respectively (16). RhoG, a ubiquitously expressed member of the Rho family of GTPases (17)(18)(19), is most similar to Rac1 and Cdc42 in sequence identity and function (20). RhoG Ϫ/Ϫ mice have elevated levels of IgG1 and IgG2b antibodies.…”