In contrast, induction of the AhCre transgene using b-napthoflavone results in rapid, high penetrance conditional gene deletion in the epithelium of the murine gastrointestinal tract. This approach allowed us to generate Lkb1-deficient intestinal epithelium in vivo and assess the consequences of Lkb1 gene function loss independently of any delayed phenotype arising in the prostate. These studies reveal,Armepavine for the first time, the functional requirement for Lkb1 in the mouse intestinal epithelium. By creating a new mouse model with conditional gene deletion of Lkb1in the epithelium of the small intestine we have shown that Lkb1 is necessary for normal intestinal cell differentiation and maturation. Lkb1 deletion not only induced an increase in the size of mucin-secreting cells, but also perturbed their morphology. Alterations in goblet cell number and elevated mucin production are common features of hamartomas characteristic of PJS and specifically have been associated with loss of heterozygosity regions within hamartomas. Normally, mucin is produced in goblet cells and Neferine ‘‘intermediate cells’’ bearing the features of both goblet and Paneth cells are rare. However, these intermediate cells were frequently observed upon Lkb1 deletion, as indicated by both lysozyme staining and electron microscopy. Secretory granules of Paneth cells from different animals tend to exhibit bipartite substructure with a peripheral halo of lower density around a large round central core of high electron density. According to histochemical studies the central core of a secretory granule contained basic protein while the peripheral halo was built with acid mucopolysaccharides. In the case of Intermediate Paneth/goblet cells observed in Lkb1-deficient intestines the mucopolysaccharide halo is abnormally large and is stained with alcian blue whereas the lysozyme filled central core is significantly smaller than in WT. This suggests that the loss of Lkb1 creates a block in the terminal differentiation of secretory cells. Intestinal cell specification is known to be directed by Notch signalling in mice, Zebrafish and Drosophila. Following Lkb1 deletion, we observed a decrease in Delta1 ligand expression in goblet and Paneth cells.