Interestingly by 16 days the phenotype has almost resolved, this suggests that it is of rapid onset but transient in nature. Analysis using qRT-PCR showed no difference in key transcripts from the major pathways implicated in the development of NAFLD comparing experimental and control animals. To gain further insight into the pathogenesis of NAFLD in the ICD-E mice we therefore examined liver transcription at 6 and 24 hour time points, using expression microarrays. Transcription of two genes involved in fatty acid uptake were up-regulated at 6 hours post-induction ; Abcd2, a gene known to be involved in the peroxisomal import of fatty acids, and the very low density lipoprotein receptor. It is also interesting to note that a previous report has indicated that Abcd2 suppresses transcription of the fatty acyl chain elongase Elovl3 and this was supported by our data at all time points. In the present study we demonstrate that over-expression of the activated mutant of Notch in the liver and small intestine of transgenic mice, but not in the liver alone, is sufficient to induce a phenotype that resembles human NAFLD coupled with mild insulin resistance. There are a several environmental and genetic models of fatty liver disease including the ob/ob mouse strain and methioninecholine STF-083010 deficient diets, however all have the disadvantage of taking place over long time periods. The model we present develops NAFLD within 96 hours and also demonstrates that expression of transcripts from the Rosa26 locus can be specifically targeted to the liver using low doses of bNF with minimal recombination in other tissues. Expression of ICD-E in the intestinal epithelium results in altered epithelial differentiation with an increased proportion of goblet cells on the villi within 24 hours, followed by a wave of apoptosis of ICD-E expressing cells in intestinal crypts. The recombinant epithelium on the villus is then lost by normal cell turnover so that by 4 days the ICD-E expressing cells have been CGS 9895 entirely replaced by wild type epithelium. These changes are associated with induction of Hes1 and Hes5, and as shown above, down-regulation of rpL29.