WILD-DERIVED GENETIC VARIATION

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This is a program to carry on a coordinated series of projects on the regulation and structure of the mammalian genome. We propose to continue to identify and characterize regulatory variants recognized as polymorphisms in intact mice, and to examine the relationship between altered gene expression studied at the protein and mRNA level and DNA sequence differences. The major focus is a study of the genetics and molecular biology of a set of androgen responsive genes, including Beta-glucuronidase, other androgen-inducible sequences in the kidney, and submaxillary gland renin. A second project concerns the examination of repetitive DNA sequences which appear within transcripts in various families of gene products. A third area in the program is the study of the genetics and molecular biology of the acute phase response in mice and the genetic characterization of the products which are part of this response. An additional element of this program contains a strong component of cell biology in the genetic and biochemical characterization of the subcellular localization of Beta-glucuronidase. This work is complemented by a genetic analysis of plasma membrane protein domains. The work is supported by the development of a series of mouse genetic resources, including new congenic strains, wild-derived stocks, and an extensive breeding program.