A knockout mouse model has been generated by targeted replacement of the protein coding exons III-V with a neomycin cassette [Pinhasov et al., 2003]. Homozygous mice are not viable and die prenatally at E8.5-9 due to a failure of cranial neural tube closure. Heterozygous mice develop normally, be it with a slight developmental delays. A detailed differential expression analysis of E9 full knockout, heterozygous and control mice in parallel with the same analysis in P19 cells showed a significant upregulation of genes involved in lipid transport, lytic vacuoles, and coagulation. Downregulated genes clustered in pathways involving regulation of transcription, organogenesis, and neurogenesis [Pinhasov et al., 2003; Mandel et al., 2007]. Typical examples in the first category include the apolipoproteins A1 and E, metalotionine 1 and neurogenin with overexpression in the range of 5–30 fold. For the second category, examples include myosin light chain 2 and neurogenin 1 with a 12-fold and 5-fold underexpression, respectively. The heterozygous knockout mouse model shows tauopathy and cognitive abnormalities as demonstrated in the passive avoidance and Morris water maze tests [Vulih-Shultzman et al., 2007; Gozes
