Figure 4. Loss of Thsd1 expression in mice disrupts the cerebrovasculature.

A, coronal T2-weighted brain MRIs and corresponding MRA images of cerebral vessels of 8-week old wild-type and Thsd1^Venus/+ mice. MRI analysis showed mild to severe dilatation of cerebral ventricles in a subset of Thsd1-mutant mice. MRA images showed poor visualization of blood flow in mice with severe ventricular dilatation. In wild-type animals, no ventricular dilatation was observed, and the vessels of the circle of Willis and emerging small vessels were well-delineated. The right panel shows schematic diagrams of normal brain regions and cerebral arteries. 3V, 3^rd ventricle; LV, lateral ventricle; EC, external capsule; CC, corpus callosum; D3V, dorsal 3^rd ventricle; HC, hippocampus; VA, vertebral artery; BA, basilar artery; MCA, middle cerebral artery; ACA, anterior cerebral artery; PCA, posterior cerebral artery; ICA, internal carotid artery; CCA, common carotid artery. B, the brain of a Thsd1^Venus/+ mouse that died suddenly at 9 weeks and that of a wild-type mouse sacrificed at 9 weeks. Both brains were from non-perfused animals and imaged under the same dissecting microscope. Unlike the wild-type brain, the Thsd1^Venus/+ brain showed massive and diffuse cerebral hemorrhage. C, H&E staining of brain slices from wild-type, Thsd1^Venus/+ and Thsd1^Venu/Venus show enlargement of lateral ventricles and extravasation of blood into the subarachnoid space (*) in a subset of mutant animals. No bleeding occurred in wild-type mice.