This is the proposal to identify the mechanisms involved in the regulation of human alcohol dehydrogenase (ADH) gene expression. Specifically: (1) Characterization of genomic clones containing human Class 1 ADH genes will be performed to analyze the structure of this multigene family. (2) DNA probes specific for the Alpha, Beta and Gamma ADH genes will be used to determine the size and amount of mRNA transcribed from these genes in various human tissues. (3) The precise locations of the transcription initiation sites for the Class I ADH genes will be determined and the promoter-regulatory regions will be subject to DNA sequence analysis. (4) The promoter-regulatory regions of the Class I ADH genes will be fused to the easily assayable chloramphenicol acetyltransferase gene and introduced into various mammalian cell lines to assess the DNA sequences necessary for ADH gene expression. Since this class of genes exhibits a very interesting pattern of tissue specific and developmental regulation, an in-depth analysis of the promoters and regulatory regions of these genes may help shed some light on how genes are turned on and off at specific times in differentiated cells. This problem is at the heart of research in developmental biology; it underlies research on the molecular basis of cancer, and it must be resolved if gene therapy is ever to come into widespread use.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
7R01AA007261-01
Application #
3111000
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1986-09-01
Project End
1988-02-29
Budget Start
1986-09-01
Budget End
1987-02-28
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
Schools of Arts and Sciences
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Mic, Felix A; Haselbeck, Robert J; Cuenca, Arnold E et al. (2002) Novel retinoic acid generating activities in the neural tube and heart identified by conditional rescue of Raldh2 null mutant mice. Development 129:2271-82
Duester, G (2001) Genetic dissection of retinoid dehydrogenases. Chem Biol Interact 130-132:469-80
Hoffmann, I; Ang, H L; Duester, G (1998) Alcohol dehydrogenases in Xenopus development: conserved expression of ADH1 and ADH4 in epithelial retinoid target tissues. Dev Dyn 213:261-70
Haselbeck, R J; Duester, G (1998) ADH1 and ADH4 alcohol/retinol dehydrogenases in the developing adrenal blastema provide evidence for embryonic retinoid endocrine function. Dev Dyn 213:114-20
Haselbeck, R J; Duester, G (1998) ADH4-lacZ transgenic mouse reveals alcohol dehydrogenase localization in embryonic midbrain/hindbrain, otic vesicles, and mesencephalic, trigeminal, facial, and olfactory neural crest. Alcohol Clin Exp Res 22:1607-13
Duester, G; Deltour, L; Ang, H L (1997) Evidence that class IV alcohol dehydrogenase may function in embryonic retinoic acid synthesis. Adv Exp Med Biol 414:357-64
Haselbeck, R J; Ang, H L; Duester, G (1997) Class IV alcohol/retinol dehydrogenase localization in epidermal basal layer: potential site of retinoic acid synthesis during skin development. Dev Dyn 208:447-53
Ang, H L; Duester, G (1997) Initiation of retinoid signaling in primitive streak mouse embryos: spatiotemporal expression patterns of receptors and metabolic enzymes for ligand synthesis. Dev Dyn 208:536-43
Satre, M A; Zgombic-Knight, M; Duester, G (1994) The complete structure of human class IV alcohol dehydrogenase (retinol dehydrogenase) determined from the ADH7 gene. J Biol Chem 269:15606-12
Duester, G (1994) Retinoids and the alcohol dehydrogenase gene family. EXS 71:279-90

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