Epithelial cells that line the intestine and the nephrons of the kidney share many common functions. The molecular mechanisms that regulate gene transcription within and between these epithelia are largely uncharacterized. The "liver" fatty acid-binding protein gene (Fabpl) 1 provides a model for investigating these mechanisms.In the adult mouse and rat, Fabpl is transcribed in hepatocytes and in polarized absorptive enterocytes, the principal epithelial cell lineage of the small intestine (1). Fabpl exhibits a cephalocaudal gradient of expression within the intestine; highest levels of its mRNA and protein products are encountered in differentiated enterocytes that overlie villi located in the middle third of the small intestine; levels diminish as one moves proximally or distally. The gene is silent in the gastric and distal colonic epithelium of both species and in all other epithelia not associated with the gastrointestinal tract.The contribution of cis-acting suppressors to maintaining this pattern of expression was revealed from studies in transgenic mice (1). Seven fusion genes were produced by sequential deletions of the proximal 4000 nucleotides of rat Fabpl's 5Ј-nontranscribed domain and linkage of each truncated product to nucleotides ϩ3 to ϩ2150 of the human growth hormone (hGH) gene. The cellular and spatial patterns of expression of each fusion gene were defined in multiple pedigrees of adult
The discovery of the Cystic fibrosis (CF) gene in 1989 has paved the way for incredible progress in treating the disease such that the mean survival age of individuals living with CF is now ~58 years in Canada. Recent developments in gene targeting tools and new cell and animal models have re-ignited the search for a permanent genetic cure for all CF. In this review, we highlight some of the more recent gene therapy approaches as well as new models that will provide insight into personalized therapies for CF.
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