Our laboratory is studying the molecular mechanisms governing tissue specific gene expression in higher animals, and the modulation of such expression by hormonal and other physiological effectors. The approach in these studies has been to fuse traditional mouse genetic resources with recombinant DNA methodologies to delineate hormonal and genetic factors regulating expression of a specific gene. At present we are concentrating our studies on the renin genes of mice. Renin is a kidney enzyme that performs a crucial role in blood pressure homeostasis.
Recent studies suggest it plays an important role in organogenesis as well.
In most mammals there is a single gene encoding renin. Mice are unusual in that the species exhibits polymorphism for chromosomes carrying either one or two renin genes. The patterns of tissue specific expression of the Renl and Ren2 genes are overlapping but distinct. Characterization of the genomic DNA sequence organization of these two genes and the transcripts which arise from them in different tissues has identified detailed structural features which may be relevant to their differential expression. Models for regulation suggested by these observations are being tested by analysis of naturally occurring genetic variants of these genes and surrogate genetic approaches that involve reintroduction of modified forms of the genes into whole animals and cells in culture, derived by transgene-mediated oncogenesis.