Fig. 2

Frem2-KO fetuses and newborn pups exhibit hemorrhagic blisters and syndactyly. A Frem2^+/+(wild-type) E15 fetus (left) with normal paws (arrow) and a Frem2^-/- (KO) littermate (right) with a blood-filled blister over the digits (arrowhead). B E16 heterozygous Frem2^+/- fetus (left) with normal paws (arrow) and E16 Frem2^-/- fetus littermate (right) with a large hemorrhagic bleb on the digits (arrowhead). C P0 Frem2^+/+ (left) and Frem2^+/- (middle) have normal paws, and a Frem2^-/- (right) has dried blood-filled blisters on both hind paws. D Newborn Frem2^-/- pups with a malformation of hind limbs, soft-tissue syndactyly, and blood-filled blisters on digits. Reference Frem2^+/+ and Frem2^+/- paws showing normal paw morphology. E Hematoxylin and eosin-stained histology section of paws from wild-type (Frem2^+/+) and several knockout (Frem2^-/-) mice with limb malformation and blood-filled blisters (arrowhead). Scale bars: A–C: 2 mm, D, E: 1 mm.