MUC19, a novel gel-forming mucin in salivary glands. Salivary mucins are well recognized to determine the viscoelastic nature of saliva and regulate its physiological activity. The molecular nature of mucin species in salivary secretions is not entirely clear. By using Hidden Markov ModeI(HMM) based genome-wide search method, we have recently identified a novel gel-forming mucin gene, MUC19 that is specifically expressed in various glandular tissues, including the salivary glands. Comparing with the known major salivary gland gel-forming mucin-MUC5B, MUC19 appears to be much larger and more abundantly expressed in salivary glands. Thus, we hypothesize that MUC19 is one of the major contributors to the viscoelastic and protective properties of salivary mucus. Changes in salivary mucus rheology may affect the phyological properties of saliva that is associated with various diseases. Because of the large gene size, the sequence of MUC19 has not been completed. And several essential molecular tools (like MUC19 specific antibodies) are still unavailable. To advance the knowledge and test the functional role of MUC 19 in salivary secretion, we propose in this pilot study to complete the genetic structure of MUC19 and to develop monoclonal antibodies specific to the gene product. In the Aim 1, we will use RT-PCR, RACE, and the molecular cloning approaches to complete the sequence and elucidate the whole genetic structure of MUC19 gene.
In Aim 2, we will characterize the expression of MUC 19 at both mRNA level and protein levels using both tissue and saliva samples. Quantitative RT-PCR as well as in situ hybridization will be used to measure the mRNA level of MUC19. MUC19 specific monoclonal antibodies will be developed and used to examine the MUC19 protein in both salivary gland tissues and salivary secretions. The success of this project will have a great impact on the field by providing immediate answer to several long-standing questions like """"""""how many mucin genes are present in the salivary secretion of health and disease?""""""""; """"""""how will different mucin species affect the physiology property of saliva?"""""""" etc. It will also generate valuable knowledge for the further exploration of the regulation of MUC 19 in various diseases. Those tools and information will be also essential for our future submission of an RO 1 grant application.
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