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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE008174-05
Application #
3221952
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1987-05-01
Project End
1992-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Shaw, Phyllis A; Zhang, Xu; Russo, Andrew F et al. (2003) Homeobox protein, Hmx3, in postnatally developing rat submandibular glands. J Histochem Cytochem 51:385-96
Shaw, P A; Yu, W H (2001) Sympathetic and parasympathetic regulation of cystatin S gene expression. Life Sci 70:301-13
Shaw, P A; Yu, W A (2000) Autonomic regulation of cystatin S gene expression in rat submandibular glands. Auton Neurosci 83:49-57
Garcia, T; Sanchez, M; Cox, J L et al. (1989) Identification of a variant form of the human estrogen receptor with an amino acid replacement. Nucleic Acids Res 17:8364
Shaw, P A; Cox, J L; Barka, T et al. (1988) Cloning and sequencing of cDNA encoding a rat salivary cysteine proteinase inhibitor inducible by beta-adrenergic agonists. J Biol Chem 263:18133-7
Barka, T; van der Noen, H; Shaw, P A (1987) Proto-oncogene fos (c-fos) expression in the heart. Oncogene 1:439-43