Yale researcher Huanjiao Jenny Zhou (Pathology) and additional School of Medicine researchers have established a Cerebral Cavernous Malformations (“CCM”) mice model which “identifies and uncovers the mechanism in which CCM3 mutation induced caveolae-Tie2 signaling contributes to CCM pathogenesis.”
Cerebral cavernous malformations (CCMs) are “vascular abnormalities which primarily occur in adulthood and lead to cerebral hemorrhage, stroke, and seizures.” CCMs can be initiated by an “endothelial cell (EC) loss of any one of the three Ccm genes: CCM1 (KRIT1), CCM2 (OSM), or CCM3 (PDCD10).”
Dr. Zhou and her research colleagues utilize mice “with a brain EC-specific deletion of Pdcd10 (Pdcd10BECKO)” which typically survive between 6-12 months. During this period, the mice develop bona fide CCM lesions in all regions of their brain which allowed the research team to study the “vascular dynamics of CCM lesions by using transcranial two-photon microscopy.”
These researchers have not only created a CCM mice model which studies vascular abnormalities, but they have also identified “caveolae-mediated Tie2 receptor signaling in the presence of its ligand Angpt2 which can offer a therapeutic approach to treat CCM disease.”
Other members of the Yale research team include: Lingfeng Qin, Quan Jiang, Haifeng Zhang, Busu Li, Qun Lin, her collaborators Katie N. Murray, Jaime Grutzendler and Wang Min in the Program of Vascular Biology and Therapeutics, Departments of Pathology, Neurobiology and Cell Biology You can read more about this exciting research in the January 25th online edition of Nature Communications.