Analysis of normal or mildly affected embryos revealed no differences between mutant and wild-type embryos in the differentiation of the developing eye until E16.5. In both genotypes, inner and outer layers of the retina displayed a comparable differentiation status, as shown, for example, at E12.5 (Figure 4a,e). At day E16.5, however, retinal layers in Ptdsr -/- embryos were much thinner than in wild-type embryos, contained fewer cells and were greatly reduced in size (Figure 4b,f). Comparison of the retinal structures of Ptdsr +/+ and Ptdsr -/- embryos revealed that all four retinal layers were present in Ptdsr-knockout mice at E16.5 (Figure 4b,f). At E18.5 (Figure 4c,g) and in neonatal animals (postnatal day P0; Figure 4d,h), the differences in retinal differentiation between Ptdsr+/+ and Ptdsr -/- mice were still evident, but the size reduction of the retinal layers was less pronounced in the knockout mice. Ptdsr-deficient animals seem to have compensated for the marked delay in cellular differentiation and expansion of retinal layers. Close examination of retinal structures revealed that the inner granular layer was still less expanded in Ptdsr-deficient animals, however, and that it contained fewer cells and was still severely underdeveloped in comparison with the corresponding retinal layer in control animals (Figure 4c,4g and 4d,4h). Thus, even mildly affected Ptdsr -/- mutants had ocular malformations with defects in differentiation of retinal structures.