| First Author | Lubeck BA | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 12 | Pages | 3163-9 |
| PubMed ID | 25283357 | Mgi Jnum | J:216433 |
| Mgi Id | MGI:5608809 | Doi | 10.1016/j.ajpath.2014.08.018 |
| Citation | Lubeck BA, et al. (2014) Blood Vascular Abnormalities in Rasa1(R780Q) Knockin Mice: Implications for the Pathogenesis of Capillary Malformation-Arteriovenous Malformation. Am J Pathol 184(12):3163-9 |
| abstractText | Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal dominant blood vascular (BV) disorder characterized by CM and fast flow BV lesions. Inactivating mutations of the RASA1 gene are the cause of CM-AVM in most cases. RASA1 is a GTPase-activating protein that acts as a negative regulator of the Ras small GTP-binding protein. In addition, RASA1 performs Ras-independent functions in intracellular signal transduction. Whether CM-AVM results from loss of an ability of RASA1 to regulate Ras or loss of a Ras-independent function of RASA1 is unknown. To address this, we generated Rasa1 knockin mice with an R780Q point mutation that abrogates RASA1 catalytic activity specifically. Homozygous Rasa1(R780Q/R780Q) mice showed the same severe BV abnormalities as Rasa1-null mice and died midgestation. This finding indicates that BV abnormalities in CM-AVM develop as a result of loss of an ability of RASA1 to control Ras activation and not loss of a Ras-independent function of this molecule. More important, findings indicate that inhibition of Ras signaling is likely to represent an effective means of therapy for this disease. |
