Rescue of Holoprosencephaly in Fetal Alcohol-Exposed Cdon Mutant Mice by Reduced Gene Dosage of Ptch1
Figure 1
Effect of reduced Ptch1 gene dosage on ethanol-induced HPE in Cdon−/− embryos: external features and lobar HPE.
(A–E) Frontal views of E14.0 embryos. About 65% of ethanol (EtOH)-treated Cdon−/−;Ptch1+/+ embryos displayed strong facial features of HPE, including a single nostril (arrowhead in C) and smooth, pointed philtrum (arrow in C). In contrast, only ∼15% of EtOH-treated Cdon−/−;Ptch1+/− embryos had external features of HPE. Two ethanol-treated Cdon−/−;Ptch1+/− embryos are shown, one that did not have external HPE features (D) and one that did (E; note the single nostril (arrowhead) and smooth, pointed philtrum (arrow)). (F-J) H&E-stained coronal sections of E14.0 embryos. Note that the ethanol-treated Cdon−/−;Ptch1+/+ embryo (H) displays continuity across the ventral midline of the forebrain (arrow), indicative of lobar HPE. Two ethanol-treated Cdon−/−;Ptch1+/− embryos are shown, one that did not have external HPE features (I) and one that did (J). Note that only the embryo that had external HPE (J) also had continuity across the ventral midline of the forebrain (arrow). See Figure S1 for saline-treated control embryos. See Table 1 for quantification.