Fig. 1

Fig. 1 liger^s430 is a hypomorphic hnf1ba zebrafish mutant and exhibits MODY5-like pancreas hypoplasia. (A,B) Merged fluorescent/bright-field micrographs of 4 dpf Tg(ptf1a:eGFP)^jh1 (arrows indicate pancreas) wild type (A, top) and liger^s430 mutants showing the most common severity of pancreas hypoplasia (A, bottom). In liger^s430 mutant embryos, the pancreas can be either nearly normal in size (B, top; <10%) or completely absent (B, bottom; <10%). (C-I) Three-dimensional rendering of the foregut endoderm of 80 hpf Tg(ptf1a:eGFP)^jh1 wild-type (C), liger^s430 (D,E), liger^s430/hnf1ba^hi2169 (F) and hnf1ba-MO injected (G-I) embryos stained for Isl1 and cadherin demonstrating complementation failure by hnf1ba^hi2169 (F) and phenocopy with Hnf1ba translational knock-down (compare D-F with G-I, respectively). (J) Genomic sequence from a liger^s430 heterozygote indicating a molecular lesion (arrow; double peek) in hnf1ba. (K) Amino acid alignment covering part of the atypical POU-specific domain of human HNF1A and HNF1B and wild-type zebrafish and liger^s430 Hnf1ba. Red font denotes the valine to glutamic acid substitution at position 147 in liger^s430. Blue font indicates amino acids affected by mis-sense mutations in MODY3 and MODY5.