Extended Data Figure 5. Exogenous delivery of Cre recombinase via AAV vector to drive combined loss of CCM function and gain of PIK3CA function results in CCM formation in the adult brain.

a, A schematic of the experimental approach in which a cranial window is created and AAV-Cre virus injected into the brains of 2 month old mice with serial imaging at post-operative days 1, 7, 10, 14, 18, and 21. b, Representative visual images of brains harvested 21 days after injection of AAV-Cre into adult animals. Dotted circles indicate the site of cranial window and AAV-Cre injection. Includes visual images displayed in Figure 1. Scale bars, 1mm. c, Serial images obtained through the same cranial window of mice of indicated genotypes following injection of AAV-Cre. iPik3ca^H1047R designation includes iPik3ca^H1047R and/or Krit1^fl/+;iPik3ca^H1047R genotypes. White arrows indicate cavernous malformations in Krit1^fl/fl;iPik3ca^H1047R mice. Black arrows indicate hypervascularity in iPik3ca^H1047R mice. d, Peri-lesional iron deposition stain in brains indicative of chronic bleed from four independent Krit1^fl/fl;iPik3ca^H1047R mice at post-op day 21. Scale bars, 200 microns.