Multimodal applications for investigating the role of mSMGP in host defense

小鼠颌下腺具有内分泌和外分泌功能，是几种生物活性多肽的合成场所，包括激素、生长因子和消化酶。虽然这些蛋白质中的许多已经得到了很好的研究和表征，但还有许多其他蛋白质的功能仍然难以捉摸。我们已经鉴定出一个基因，我们将其蛋白称为小鼠颌下腺蛋白(MSMGP)，该基因在该腺体中高度表达，其功能尚未阐明。MSMGP还存在于唾液和其他体液中，如泪水、汗液和精囊分泌物。我们已经证明mSMGP与一些人和小鼠口腔细菌株结合。这些观察，以及来自人类同源物的一些线索，可以与CD4分子结合并抑制T淋巴细胞凋亡，使我们假设小鼠颌下腺蛋白mSMGP在抵御入侵生物和感染的先天性和免疫宿主防御中发挥作用。为了解决mSMGP在体内的功能，我们建立了第一个小鼠mSMGP基因敲除模型。通过对基因敲除小鼠的组织病理学分析和一系列细菌研究，我们目前的目标是完全确定mSMGP功能丧失的表型，并检测其在体内和体外与细菌的相互作用。到目前为止，通过口腔污染对入侵生物或感染的保护作用还知之甚少，因此拟议的研究是极少数从口腔角度探讨感染现象的研究之一。这项研究将对mSMGP的功能和生物学产生重要的见解，从而有助于进一步了解下颌下生物学。对我们的分子和免疫学研究至关重要的是常规使用微量平板阅读器和解剖显微镜。这种设备在培训和教学中也很重要。同样重要的是，对细菌生长所需的细菌摇床的要求。目前，我们的实验室没有这种设备，这阻碍了这一项目的进展。

The mouse submaxillary (submandibular) gland exhibits both endocrine and exocrine functions, and is the site of synthesis of several biologically active polypeptides, including hormones, growth factors, and digestive enzymes. Although many of these proteins are well studied and characterized, the function of yet many others remain elusive. We have identified a gene, whose protein we termed the mouse submaxillary gland protein (mSMGP), that is highly expressed in this gland and whose function is yet to be elucidated. mSMGP is also found in saliva and other bodily fluids such as tears, sweat and secretions from the seminal vesicle. We have shown that mSMGP binds some strains of both human and mouse oral bacteria. These observations, as well as some clues that have come from a human homologue which can bind to the CD4 molecule and inhibit T lymphocyte apoptosis, led us to hypothesize that the mouse submaxillary gland protein, mSMGP, plays a role in both innate and immune host defense against invading organisms and infection. To address mSMGP function in vivo, we have generated the first mouse mSMGP knockout model. Using histopathological analysis of the knockout mouse and a series of bacterial studies, our current objectives is to fully define the phenotype attributed to loss of mSMGP function, and to examine its interaction with bacteria both in vivo and in vitro. Protection against invading organisms or infection via oral contamination is to date, poorly understood and thus the proposed studies are among the very few that approach the infection phenomenon from an oral perspective. This study will yield critical insights into the function and biology of the mSMGP, and consequently contribute further knowledge about submandibular biology. Vital to our molecular and immunological studies is the routine use of a microplate reader as well as a dissecting microscope. This equipment is also important for training and teaching purposes. Equally critical is the requirement for a bacterial shaker for growing bacteria. At the present time we do not have this equipment in our laboratory and this is impeding on the progress of this project.