Abnormal head development in the OVE1070 FGF9 transgenic mice. Panel A shows a schematic representation of the FGF9 transgene. The coding region of mouse Fgf9 cDNA was inserted between the αA-crystallin promoter (αAp) and an intron and polyadenylation sequence derived from SV40 virus . The microinjection fragment was generated by SstII digestion. The SV40 sequences were used to make a riboprobe for detection of expression of the transgene. (B and C) Three day old nontransgenic (NT) and FGF9 transgenic mice are shown. The heads of the transgenic mice are 'dome' shaped (C). The OVE1070 transgenic mice often show unfused eyelids at birth (C). (D-K) Skeletal preparations of the FGF9 transgenic mice reveal an expansion in the cartilage territory in the head region. Alcian blue and Alizarin red stained E15 (D and E), P3 (F and G), P10 (H and I) and P30 (J and K) heads are shown. Cartilage is stained blue and bone red. The insets in panels D and E are higher magnifications of the frontal and parietal bones in the nontransgenic and transgenic mice respectively. The insets in panels F-I are rear views. The insets in panels J and K are top views. An expansion in the cartilage territory is seen in the FGF9 transgenic mice. Parietal bone (p) is affected in the transgenic skulls but the coronal suture is still present (E inset, arrow). Frontal (f) and occipital bone formation appear to be unaffected (E and G insets). A hole forms in the skull of the FGF9 transgenic mice that is visible by P3 (G inset, arrow) and is seen to persist at P10 (I inset, arrow). The red stain visible at the arrow in the inset in panel G is bone at the base of the head, which is visible since the skull and the brain are transparent after staining and clearing. The cartilage territory is replaced by bone by P30 (K and inset). Scale bar: 1 mm in D and E; 1.6 mm in F and G; 2.5 mm in H-K.