The aim of this work is to investigate the mechanisms controlling the expression of a multi-gene family, namely the class I MHC genes. The miniature swine has been chosen as an experimental model because there are only 7 members of the family, of which 6 have been isolated. Five have been extensively structurally characterized. To address the question of the molecular regulation of the expression of the class I MHC genes, two approaches have been taken: 1) analysis of in vivo patterns of expression of each of the genes in a variety of tissues both in the miniature swine and in transgenic mice containing only a single swine gene, and 2) characterization of regulatory elements associated with these genes. Three categories of MHC genes have been identified this way: 1) A set of closely related genes each of which are expressed in L cells and in nearly all swine somatic tissues, although at different levels. At least one of these genes is also expressed in a transgenic mouse with the same tissue distribution as in the swine. These genes encode products which are expressed on the cell surface and are able to bind a monoclonal antibody which recognizes a common determinant, also found on classical transplantation antigens. 2) A distantly related gene which is expressed both in L cells and in vivo but whose pattern of expression is distinct from that of transplantation antigens. 3) A set of genes which is expressed neither in L cells nor in vivo. Regulatory sequences within one of the transplantation antigen genes have been identified by generating a series of 5' end deletion mutants. The transcriptional promoter has been functionally identified as well as an interferon-responsive element. In addition, novel positive and negative regulatory sequence elements have been identified. It has been further shown that these elements function through the binding of transacting factors.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB005115-05
Application #
3939247
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code