SALIVARY MUCOUS CELL GENE EXPRESSION

产品说明：阐明控制唾液外分泌细胞分化的机制对于开发基于细胞的治疗方法来治疗头颈部放疗后或患有自身免疫性疾病的患者是必要的。我们正在研究NFS/N-sld小鼠，以阐明唾液粘液细胞分化的因素。在初步研究中，我们已经确定了一种新的小鼠基因（mSLG MUC）编码的无粘蛋白表达在小鼠舌下腺和生物信息学证据的同线人类同源。由于这些脱粘蛋白可能代表粘液细胞特异性的基因产物，因此它们是研究粘液细胞分化和基因表达的极好焦点。因此，我们将：1）描述mSLG MUC脱粘蛋白基因的基因组结构及其组织和细胞特异性表达。我们还将测试假设，一个假定的人类基因同线的mSLG MUC表达在人类唾液粘液腺，如果是这样，描绘其基因组组织。我们将sld突变基因定位到一个基因贫乏的关键区域（15号染色体上=1.2兆碱基），其中包括mSLG MUC。我们将：2）确定携带sld突变的基因，并研究与sld表型相关的病变。在sld小鼠中粘液细胞表达的增加似乎与无粘蛋白转录本和粘蛋白糖蛋白的腺体稳态水平有关。我们的综合数据表明sld表型与脱粘蛋白的表达有关。有趣的是，最近已经确定，神经内分泌细胞，嗜铬粒蛋白A的主要分泌产物，作为一个限速步骤的分泌颗粒的生物合成和调节外分泌的功能。以此类推，我们证明舌下无粘蛋白具有促进粘液细胞终末分化的功能。因此，我们将：3）确定调节脱粘蛋白转录物的稳态水平的机制，并且还测试mSLG MUC脱粘蛋白功能促进粘液细胞表型的终末分化的假设。从这些综合研究中，我们表征了一种新的基因，mSLG MUC，这可能是唯一已知的基因选择性表达在唾液粘液细胞。我们还将评估Mslg MUC在粘液细胞终末分化中的作用，并确定其与sld突变的关系。此外，将验证表达唾液无粘蛋白的新型人类基因的表达，并且如果表达，将是未来研究的焦点，以确定调节其表达的机制。

DESCRIPTION: Elucidation of mechanisms controlling differentiation of salivary exocrine cells is required for development of cell-based therapeutics to treat patients after head/neck radiation or with autoimmune diseases. We are studying NFS/N-sld mice to elucidate factors in the differentiation of salivary mucous cells. In preliminary studies, we've identified a novel mouse gene (mSLG MUC) encoding the apomucin expressed in murine sublingual glands and have bioinformatic evidence for a syntenic human homologue. As these apomucins may represent gene products specific for mucous cells they are excellent focal points to study mucous cell differentiation and gene expression. We thus will: 1) Delineate the genomic organization of the mSLG MUC apomucin gene and its tissue and cell specific expression. We will also test the hypothesis that a putative human gene syntenic to mSLG MUC is expressed in human salivary mucous glands, and if so, delineate its genomic organization. We genetically mapped the sld mutation to a gene-poor critical region (=1.2 megabases on chromosome 15) that includes mSLG MUC. We will: 2) Determine the gene harboring the sld mutation and investigate the associated lesion responsible for the sld phenotype. The increase in mucous cell expression in sld-mice appears related to both glandular steady-state levels of apomucin transcripts and mucin glycoproteins. Our combined data indicate the sld phenotype is linked to expression of the apomucin. Interestingly, it has recently been determined that the major secretion product of neuroendocrine cells, chromogranin A, functions as a rate-limiting step in the biogenesis of secretory granules and regulated exocrine secretion. By analogy, we posit the sublingual apomucin functions to promote terminal differentiation of mucous cells. We will therefore: 3) Determine mechanism[sl by which steady-state levels of apomucin transcripts are regulated and also test the hypothesis that the mSLG MUC apomucin functions to promote the terminal differentiation of the mucous cell phenotype. From these combined studies, we characterize a novel gene, mSLG MUC, that likely represents the only known gene to be expressed selectively in salivary mucous cells. We also will evaluate the role of Mslg MUC in the terminal differentiation of mucous cells and determine its relationship to the sld mutation. Moreover, expression of a novel human gene expressing a salivary apomucin will be verified, and if expressed, would be the focus of future studies to determine mechanisms regulating its expression.