Fig. 7

Mutation of the nf2 gene results in choledochal cyst formation. (A) hi³³³² mutants contain an insertion in the intron upstream of the start site of the nf2 gene. Grey boxes indicate exons, lines indicate introns; ATG is the start codon. (B) cDNA prepared from day 5 phenotypically wild-type embryos and their mutant siblings from hi³³³² was amplified nf2 and actin primers. (C-I) Hematoxylin and Eosin-stained histological sections through wild-type (D,E,G) and mutant (D,F,H,I) liver (C-F), gallbladder and common bile duct (G-I). Other than the large spaces in the mutant livers (asterisk in D), the wild-type and mutant livers appear similar (E,F). The common bile duct is cystic in nf2 mutant embryos (H,I). The section in I illustrates the gallbladder-ductal junction, and the formation of a diverticuli (asterisk) in the common bile duct of this embryo. Scale bars: 50 µm in C,D; 5 µm in E-I. (J-N) PED6 labeling of wild-type (J,L) and nf2 mutant (K,M,N) day 7 embryos. The gallbladder is a brightly labeled oblong or spherical organ in wild-type embryos, whereas it is always oblong in mutant embryos. The common bile duct (arrows) is dilated and diverticuli (asterisk in N) form in nf2 mutant embryos. (O) Quantification of ductal morphology in wild-type, mutant and nf2 morphant day 7 embryos fed PED6. P<0.003 for the comparison of the number of embryos with dilated bile ducts in wild-type and mutant embryos (not shown). Some mutant and morphant embryos do not accumulate any PED6 in their gallbladder (no label). gb, gallbladder; cbd, common bile duct.