MUC19, a novel gel-forming mucin in salivary glands

描述：MUC19，唾液腺中一种新的凝胶形成粘蛋白。 唾液粘蛋白被公认为可以确定唾液的粘弹性性质并调节其生理活性。唾液分泌物中粘蛋白种类的分子性质尚不完全清楚。通过基于隐马尔可夫模型(HMM)的全基因组搜索方法，我们最近发现了一个新的凝胶形成粘蛋白基因MUC19，该基因在包括唾液腺在内的各种腺体组织中特异表达。与已知的主要唾液腺凝胶形成粘蛋白-MUC5B相比，MUC19似乎更大，在唾液腺中表达更丰富。因此，我们假设MUC19是唾液粘液的粘弹性和保护性的主要贡献者之一。唾液粘液流变学的改变可能会影响唾液的生理特性，这与各种疾病有关。由于基因大小较大，MUC19的序列尚未完成。一些基本的分子工具(如MUC19特异性抗体)仍然不可用。为了进一步了解MUC19在唾液分泌中的功能作用，我们在这项初步研究中建议完善MUC19的遗传结构，并开发针对该基因产物的单抗。在目标1中，我们将使用RT-PCR、RACE和分子克隆的方法来完成MUC19基因的测序，并阐明MUC19基因的完整遗传结构。在目标2中，我们将使用组织和唾液样本来表征MUC 19在mRNA和蛋白质水平的表达。定量RT-PCR和原位杂交将用于检测MUC19的mRNA水平。将开发MUC19特异性单抗，并用于检测唾液腺组织和唾液分泌物中的MUC19蛋白。该项目的成功将对该领域产生重大影响，为健康和疾病的唾液分泌中存在多少粘蛋白基因，以及不同的粘蛋白物种将如何影响唾液的生理特性等几个长期存在的问题提供即时答案。这也将为进一步探索MUC 19在各种疾病中的调控提供有价值的知识。这些工具和信息对于我们未来提交RO 1拨款申请也是必不可少的。

DESCRIPTION: 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.