AGE-RELATED RESPONSE OF SALIVARY GLANDS TO ISOPROTERENOL

建议利用唾液腺作为体内模型， 研究调节β-肾上腺素能- 受体介导的两种不同基因在同一细胞中的表达 细胞，一种在正常发育（LM）期间表达， 另一个是原癌基因（c-fos）， 这是未知的。 增加对这些因素的了解 调节基因的表达，所述基因在 唾液腺的正常发育，以及原癌基因， 其中的一种可以被同一种β-肾上腺素能受体诱导表达， 激动剂，以及它们的表达可能被改变的方式 对于理解这两种现象的理性方法来说， 正常和异常的细胞机制。 我们最近克隆了编码LM分泌型的cDNA， 蛋白质，并建议使用克隆来检查以下内容 具体目标： I. 以确定表达的发育模式， LM基因，并将这种表达与指标相关， 分化和生长的唾液腺在体内（两者 生理和刺激），以及 二. 为了确定LM基因的数量，分离和 表征LM基因，表征LM mRNA，和 染色体定位LM基因，和 三. 研究β-肾上腺素能受体 激动剂早熟诱导基因（LM）表达， 在正常的发展过程中，比较和对比这些 与原癌基因（c-fos）的机制， 已知在正常发育过程中表达，但也可以是 被同一种媒介诱导表达。 唾液腺生后发育的研究概况 将是未来实验的基础， 衰老和衰老动物中的参数。

It is proposed to utilize salivary glands as an in vivo model for investigating the mechanism(s) regulating the beta-adrenergic- receptor mediated expression of two different genes in the same cell, one which is expressed during normal development (LM) and the other a proto-oncogene (c-fos), the developmental pattern of which is unknown. An increased understanding of the factors regulating the expression of a gene which is expressed during normal development of salivary glands, and a proto-oncogene both of which can be induced to express by the same beta-adrenergic agonist, and the manner in which their expression may be altered is essential for rational approaches toward understanding both normal and aberrant cellular mechanisms. We have recently cloned the cDNA coding for the LM secretory protein and propose to use the clone to examine the following specific aims: I. to determine the developmental pattern of expression of the LM gene and to correlate this expression with indices of differentiation and growth of salivary glands in vivo (both physiologic and stimulated), and II. to determine the number of LM gene(s), to isolate and characterize the LM gene(s), to characterize the LM mRNA, and chromosomally localize the LM gene(s), and III. to examine the mechanism(s) by which a beta-adrenergic agonist precociously induces a gene (LM) which is expressed during normal development, and compare and contrast these mechanisms with those of a proto-oncogene (c-fos) which is not known to be expressed during normal development, but can be induced to express by the same agent. The studies outlined on postnatal development of salivary glands will be the basis of future experiments designed to examine these parameters in aging and senescent animals.