LacZ cassette into the VEGFR-3 locus (11). The 3-kb

Kpn I—Not I and Bam HI—Kpn I fragments from 129SV mouse genomic DNA library (lFIX II; Stratagene) were used as the arms of the targeting vector (Fig. 1). The gene-targeting event was conÞrmed by Southern (DNA) blot analysis (Fig. 1) (D. J. Dumont et al., data not shown), and two independent embryonic stem cell lines were used to make heterozygous mice through blastocyst injection. Wild-type, heterozy-gous, and homozygous embryos and mice were iden-tiÞed by Southern blot analysis of yolk sac and tail DNA, respectively