Abstract

The major objective of the proposed research is to study the mechanism by which the expression of DNA is regulated. This will be done by injecting genes or modified genes into mouse ova. The effect of the DNA will be assayed in the ova following in vitro culture, or in mice that develop from the injected ova following transfer to foster mothers.
The specific aims are: (1) Determine the nucleotide sequenes involved in regulation of metallothionein-1 gene transcription by heavy metals and glucocorticoids, (2) Determine the factors that influence the integration of genes into the genome following their injection into the nucleus of the fertilized one-cell mouse ovum and the expression of these genes in animals developing from the ova, (3) Determine whether a genetic defect in mice can be corrected by introducing appropriate genes determine what DNA sequences are important for regulation of a specific gene and should enable us to study the effect important biological changes, e.g. development and aging, have on the expression of several gene modification. In addition to the information we will obtain about gene regulation, the introduction of new genes into an animal will provide information of fundamental importance in determining the possible usefulness of gene therapy in the treatment of human disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017321-04
Application #
3314299
Study Section
Reproductive Biology Study Section (REB)
Project Start
1983-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Behringer, R R; Lewin, T M; Quaife, C J et al. (1990) Expression of insulin-like growth factor I stimulates normal somatic growth in growth hormone-deficient transgenic mice. Endocrinology 127:1033-40
Pinkert, C A; Manz, J; Linton, P J et al. (1989) Elevated PC responsive B cells and anti-PC antibody production in transgenic mice harboring anti-PC immunoglobulin genes. Vet Immunol Immunopathol 23:321-32
Ryan, T M; Behringer, R R; Martin, N C et al. (1989) A single erythroid-specific DNase I super-hypersensitive site activates high levels of human beta-globin gene expression in transgenic mice. Genes Dev 3:314-23
Ryan, T M; Behringer, R R; Townes, T M et al. (1989) High-level erythroid expression of human alpha-globin genes in transgenic mice. Proc Natl Acad Sci U S A 86:37-41
Storb, U; Engler, P; Manz, J et al. (1988) Expression of immunoglobulin genes in transgenic mice and transfected cells. Ann N Y Acad Sci 546:51-6
Mathews, L S; Hammer, R E; Behringer, R R et al. (1988) Growth enhancement of transgenic mice expressing human insulin-like growth factor I. Endocrinology 123:2827-33
Manz, J; Denis, K; Witte, O et al. (1988) Feedback inhibition of immunoglobulin gene rearrangement by membrane mu, but not by secreted mu heavy chains. J Exp Med 168:1363-81
Tsang, H; Pinkert, C; Hagman, J et al. (1988) Cloning of a gamma 2b gene encoding anti-Pseudomonas aeruginosa H chains and its introduction into the germ line of mice. J Immunol 141:308-14
Gollahon, K A; Hagman, J; Brinster, R L et al. (1988) Ig lambda-producing B cells do not show feedback inhibition of gene rearrangement. J Immunol 141:2771-80
Mathews, L S; Hammer, R E; Brinster, R L et al. (1988) Expression of insulin-like growth factor I in transgenic mice with elevated levels of growth hormone is correlated with growth. Endocrinology 123:433-7

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