Heterozygosity for a Col4a1 null allele causes rare, mild cerebrovascular abnormalities. (A) Representative images of Prussian blue-stained coronal brain sections from 6-mo-old mice challenged with treadmill exercise showing the absence of staining in all R26^Flpe;Col4a1^+/+ mice (left) and most Col4a1^+/− mice (middle left). We observed evidence of small ICH in 2 out of 12 Col4a1^+/− mice (middle right, and black arrows in higher magnification of boxed area). An example image from a Col4a1^+/G1344D mouse was also shown (right). Scale bar = 1 mm and 100 μm in low magnification images and inserts, respectively. n = 7 and 12 for R26^Flpe;Col4a1^+/+ and Col4a1^+/− samples, respectively. (B) Representative images of coronal brain sections from 1-mo-old mice injected with 3 kDa fluorescein-conjugated Dextran. While no extravasation was detected in R26^Flpe;Col4a1^+/+ mice (left), most of the sections from Col4a1^+/− mice had negligible fluorescein signals indicating minimal or no leakage (middle left), and two sections out of three from one Col4a1^+/− brain had one and two leakage sites, respectively (middle right, white arrowhead in higher magnification of boxed area). An example image from a Col4a1^+/G1344D mouse showing multifocal lesions (white arrowheads) across the entire brain was also shown (right). Scale bar = 1 mm and 100 μm in low magnification images and inserts, respectively. n = 3 per genotype.