The working hypothesis of the principal investigator is that the functional P450 gene(s) orthologous to rat and rabbit 2G1 are present in the human genome and highly conserved regulatory sequences will be present in the 5' flanking region of rat, rabbit, and human 2G1 genes, that human 2G1 is expressed only in olfactory chemosensory epithelium and is active in the metabolism of sex steroid hormones as well as odorants and pheromones, and that regulation of 2G1 gene expression during chemically induced degeneration and subsequent regeneration of olfactory neurons involves tissue-specific transcription factors and unique regulatory elements int the 5' flanking region of the 2G1 gene. Toward the testing of this hypothesis, the principal investigator has 3 specific aims: 1) To determine the gene structure of human 2G1 and the sequence of 5' regulatory regions of human, rat, and rabbit 2G1 genes; 2) to determine the catalytic activity and cellular distribution of human 2G1; 3) to study the regulation of 2G1 expression during chemically induced degeneration and subsequent regeneration of olfactory epithelium in rats. The principal investigator has noted that there is a loss of P450 2G1 after olfactory neuronal cell loss and reactivation following regeneration. Since the P450 is expressed in non-neuronal cells, the control of expression during regeneration is intriguing. The P450 enzymes are in great abundance in the olfactory epithelium and its function in olfaction is an important topic to explore.
