The major objective of the proposed research is to introduce a new gene into one or more large animal species and to study the effects of the foreign gene. Studies with mice have demonstrated the usefulness of the gene transfer technique to study gene regulation and development. However, the transfer of new genes into large animals will allow several types of investigations not readily undertaken in mice. There are two major specific aims: (1) To introduce a functional metallothionein-growth hormone gene into a large animal such as a rabbit, sheep, goat, pig or cow. This gene construction functions well in mice and would provide and opportunity to extend the gene transfer system to large animals. In addition, studies on the effect of the new gene on several aspects of growth, lactation, and endocrine balance would be facilitated in large animals. (2) To introduce a functional human blood clotting factor IX gene into a large animal. The presence of a functioning factor IX gene in various tissues of several species will allow us to examine the effect of tissue type and species on critical biochemical reactions, such as Gamma-carboxylation and glycosylation, that are important in processing protein. Large animals are required to provide the substantial amounts of tissue needed for the protein processing assays. Since transgenic animals should synthesize an identical protein in several tissues of a species and also in the different species, these animals will provide a unique opportunity to study the role of tissue factors in protein processing.
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