| First Author | Tamehiro N | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 6 | Pages | e0131047 |
| PubMed ID | 26114424 | Mgi Jnum | J:233791 |
| Mgi Id | MGI:5788064 | Doi | 10.1371/journal.pone.0131047 |
| Citation | Tamehiro N, et al. (2015) Overexpression of RhoH Permits to Bypass the Pre-TCR Checkpoint. PLoS One 10(6):e0131047 |
| abstractText | RhoH, an atypical small Rho-family GTPase, critically regulates thymocyte differentiation through the coordinated interaction with Lck and Zap70. Therefore, RhoH deficiency causes defective T cell development, leading to a paucity of mature T cells. Since there has been no gain-of-function study on RhoH before, we decided to take a transgenic approach to assess how the overexpression of RhoH affects the development of T cells. Although RhoH transgenic (RhoHtg) mice expressed three times more RhoH protein than wild-type mice, beta-selection, positive, and negative selection in the thymus from RhoHtg mice were unaltered. However, transgenic introduction of RhoH into Rag2 deficient mice resulted in the generation of CD4+ CD8+ (DP) thymocytes, indicating that overexpression of RhoH could bypass beta-selection without TCRbeta gene rearrangement. This was confirmed by the in vitro development of DP cells from Rag2-/-RhoHtg DN3 cells on TSt-4/Dll-1 stroma in an Lck dependent manner. Collectively, our results indicate that an excess amount of RhoH is able to initiate pre-TCR signaling in the absence of pre-TCR complexes. |
