MUC19, a novel gel-forming mucin in salivary glands

描述：MUC 19，一种唾液腺中的新型凝胶形成粘蛋白。 唾液粘蛋白被公认为决定唾液的粘弹性并调节其生理活性。唾液分泌物中粘蛋白种类的分子性质尚不完全清楚。通过使用隐马尔可夫模型（HMM）为基础的全基因组搜索方法，我们最近发现了一种新的凝胶形成粘蛋白基因，MUC 19，它特异性地表达于各种腺体组织，包括唾液腺。与已知的大唾液腺凝胶形成粘蛋白MUC 5 B相比，MUC 19似乎更大，在唾液腺中表达更丰富。因此，我们假设MUC 19是唾液粘液的粘弹性和保护性质的主要贡献者之一。唾液粘液流变学的变化可能会影响与各种疾病相关的唾液的生理特性。由于MUC 19的基因大小较大，其序列尚未完全确定。一些基本的分子工具（如MUC 19特异性抗体）仍然不可用。为了进一步了解和测试MUC 19在唾液分泌中的功能作用，我们在这项初步研究中建议完成MUC 19的遗传结构，并开发特异性针对该基因产物的单克隆抗体。目的一：利用RT-PCR、RACE和分子克隆等方法，对MUC 19基因进行全序列测定，阐明MUC 19基因的遗传结构。在目标2中，我们将使用组织和唾液样品在mRNA水平和蛋白水平上表征MUC 19的表达。定量RT-PCR以及原位杂交将用于测量MUC 19的mRNA水平。将开发MUC 19特异性单克隆抗体并用于检查唾液腺组织和唾液分泌物中的MUC 19蛋白。该项目的成功将对该领域产生重大影响，它将立即回答几个长期存在的问题，如“健康和疾病的唾液分泌中存在多少粘蛋白基因？不同种类的粘蛋白对唾液的生理特性有何影响？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将来提交RO 1赠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.