Some Ptdsr -/- mice (4.5 %) also displayed extensive brain malformations that resulted in externally visible head abnormalities, with occasional ectopic tissue outside the skull or exencephaly (Figure 1f,h). Histological analysis revealed an extensive hyperplasia of brain tissue with herniation of brain tissue either through the skull-cap or through the ventral skull (Figure 3d,j). In the most severe cases, expansion of brain tissue in mutant mice resulted in further perturbations of cortical structures (Figure 3d,j). Of note, a similar brain phenotype was observed in the Ptdsr-deficient mouse line generated by Li and colleagues [31].