Dept. of Biological Sciences

Michael R. Felder

Professor of Biological Sciences
Ph.D., 1970, University of California, Davis
803-777-5135
felder@biol.sc.edu

Mouse Molecular Genetics. Structure and Regulation of Mouse Alcohol Dehydrogenase and Cytochrome p450 Genes. Alcohol Metabolism.

We are interested in the regulation of alcohol dehydrogenase genes in mice and the biochemistry of ethanol metabolism. Inbred strains of mice differ in activity of liver alcohol dehydrogenase and this difference has been shown to be under single gene control. The strain difference in enzyme activity is due to regulatory differences between strains in that high activity strains contain more enzyme protein than low activity strains and synthesize the enzyme at a faster rate. In addition to this genetic control, liver alcohol dehydrogenase is developmentally regulated and is androgen inducible in kidney. Strains of deermice that are genetically deficient for alcohol dehydrogenase have been developed and are being used to study genetic regulation of this enzyme and its physiological role in ethanol metabolism.

Selected Publications:

Szalai, G., Duester, G., Friedman, R., Jia, H., Lin, S., Roe, B. A. and Felder, M. R. 2002. Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes. Eur. J. Biochem. 269, 224-232.

Szalai, G., Xie, D., Wassenich, M., Veres, M., Ceci, J. D., Dewey, M. J., Molotkov, A., Duester, G., and Felder, M. R. 2002. Distal and proximal cis-linked sequences are needed for the total expression phenotype of the mouse alcohol dehydrogenase 1 (Adh1) gene. 2002. Gene 291, 259-270.

Dolney, D. E. A., Szalai, G., Duester, G., and Felder, M. R. 2001. Molecular analysis of genetic differences among inbred strains controlling tissue expression pattern of alcohol dehydrogenase 4. Gene 267, 145-156.

Dolney, D. E. A., Szalai, G., and Felder, M. R. 2001. Differences in charge and kindetic properties of alcohol dehydrogenase 4 from C57BL/6 mice compared to other inbred strains are associated with a cysteine 120 to arginine 120 substitution. Biochem. Genet. 39, 239-250.

Szalai, G., Duester, G., Friedman, R., Jia, H., Lin, S., Roe, B. A., and Felder, M. R. 2001. Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes. Eur. J. Biochem. 269, 224-232.

Zheng, Y. -W. and M. R. Felder. 1997. Genetic mapping of a possible new alcohol dehyrogenase sequence to mouse chromosome 3 at the Adh-1/Adh-3 complex. Biochemical Genetics. 35:105-117.

Xie, D., P. Narasimhan, Y. -W. Zheng, M. J. Dewey, and M. R. Felder. 1996. Ten kilobases of 5' - flanking region confers proper regulation of the  mouse alcohol dehydrogenase-1 (Adh-1) gene in kidney and adrenal tissue of transgenic mice. Gene 181:173-178.

Zheng, Y. -W., M. Bey, H. Liu, and M. R. Felder. 1993. Molecular basis of the alcohol dehydrogenase negative deermouse:  Evidence for deletion of the gene for class I enzyme and identification of a possible new enzyme. J. Biol. Chem. 268:24933-24939.

Davis, J. F. and M. R. Felder. 1993. Mouse Ethanol-Inducible Cytochrome P450 (P450IIE1).  Characterization of cDNA clones and testosterone induction in kidney tissue. J. Biol. Chem. 268:16584-16589.

Tussey, L. and M.R. Felder. 1989. Tissue-specific genetic variation in the level of mouse alcohol dehydrogenase is controlled transcriptionally and kidney and posttranscriptionally in liver. Proc. Natl. Acad. Sci. U.S.A. 86:5903-5907.

Felder, M.R., G. Watson, M.D. Huff, and J.D. Ceci. 1988. Mechanism of induction of mouse kidney alcohol dehydrogenase by androgen. J. Biol. Chem. 263:14521-14537.

Ceci, J.D, Y.-W. Zheng, and M.R. Felder. 1987. Molecular analysis of mouse alcohol dehydrogenase: nucleotide sequence of the Adh-1 gene and genetic mapping of a related nucleotide sequence to chromosome 3. Gene 59:171-182.

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