Fig. 2. Phenotypical consequences of homozygous IRES-lacZ knock-in into the Vegf locus. +/+, wild type; –/–, Vegf^lo/lo. (E-H) -PECAM specific immunohistochemistry; (I-T) Haematoxylin/Eosin-stained sections. (A,B,E,F) In the 8.5 dpc yolk sac, defects in vascularisation (B,F) lead to formation of endothelial cell-lined ‘lacunae’ (arrows). (I,J) Few ‘blood islands’ (arrowheads) devoid of primitive erythrocytes are observed in Vegf^lo/lo embryos (J) in comparison with wild-type littermates (I). (C,D) Growth retardation in Vegf^lo/lo (D) becomes obvious shortly before death at 8.5-9.0 dpc (compare with wild type in C). (G,H,K,L) Lumen formation of the dorsal aortae is impaired (H,L) in the aorta-gonad-mesonephros region at 8.5 dpc when compared with wild type (G,K). Dorsal aortae are indicated with asterisks (G,H) and arrowheads (K,L). (M-P) Intra-embryonic defects with delayed heart development and lack of blood cells in the sinus venosus (sv) (N,P) compared with wild type (M,O). Endocardium (enc) and cardinal veins (white arrowheads) are formed properly. Dorsal aortae are indicated with black arrowgeads. (Q-T) Phenotypic alterations in the yolk sac are obvious as early as 8.0 dpc. Embryos show a reduction in the number of blood islands and those that are present are devoid of primitive erythrocytes.