Decreased VIPergic innervation in the duodenum of C57Bl/6 CF mice

Cystic Fibrosis (CF) is the most common fatal genetic disease in white populations. It is caused by a mutation (change) in the CFTR gene (Cystic Fibrosis Transmembrane conductance Regulator) which encodes for the CFTR protein. This protein controls the flow of salt and fluids in and out of our cells. If CFTR is dysfunctional, it causes a buildup of thick and viscous mucus that covers the lungs and the gut, leading to malabsorption of nutrients and severe airway disease with chronic inflammation and bacterial infection. Previous studies from the Chappe lab indicate that the Vasoactive Intestinal Peptide (VIP), an important natural peptide (a form of a very tiny protein) of the body that controls CFTR to maintain healthy lungs and digestive system, could play a major role in CF disease development and progression. Unfortunately, VIP which is normally released by nerves surrounding the lungs, intestine and pancreas, appears to be missing or poorly present in CF. In the present study, I have measured the amount of VIP in the lung, sweat glands, intestine, pancreas and salivary glands of 8- to 17-week-old CF mice compared to same age healthy tissues. I am also investigating changes in nerves that produce VIP. The study of VIP in CF mice will allow us to verify the findings in humans with CF and consequently use the mouse model as an appropriate model for testing VIP as a cure. Since VIP is a key peptide for the function of the CFTR protein, this research will result in new knowledge of an important under-studied aspect of the disease and will provide some clues for the development of a VIP-based therapy to treat CF.