STRUCTURE EXPRESSION REGULATION OF MICE/HUMAN IA GENES

  • David, Chella S, (PI)

Project: Research project

Project Details

Description

In this proposal, studies will be continued on the mouse MHC class II la
antigens and a new program to study human class II genes will be
initiated. In the mouse system, transgenic mice will be generated with
exon shuffled la genes from the A(K,A), A(Q,A) and E(K,A) genes to
determine the site on the la molecule which presents Mls antigen and super
antigens to the T cells. The precise site on the la molecule will be
further narrowed down by generating la mutant genes by site directed
mutagenesis and producing transgenic mice with them. Regulation of
A/alpha and E/beta genes will be determined by constructing la genes with
different promotor regions and generating transgenic mice to examine the
tissue expression. The importance of the N-linked oligosaccharides in the
function of la molecules will be determined by mutating the
oligosaccharide attachment sites on the la genes and producing transgenic
mice with them. The recombination hot spot which has been identified in
the E alpha gene will be determine by DNA sequencing. These studies in
the mouse system will increase our understanding of the structure/function
relationship of la genes. Using the transgenic technology, mice
expressing human class II genes will be generated for further serological
characterization and definition of determinants, specificities and
epitopes on the human class II molecules and localization to specific
chains and domains. These transgenic mice would also be utilized to study
the regulation of human la genes. Studies will be initiated using anti-
sense RNA to determine the feasibility of downregulating endogenous class
II genes in vivo. Finally, structure/function of human class II genes
will be studied using the transgenic mice. Since the class II genes play
such a crucial role in immune response, self versus non-self regulation,
susceptibility to disease and cancer, the information we gain from the
mouse and human la genes and their products are critical to understanding
the immune system and devising methods of disease prevention and immune
therapy. Eventually transgenic mice will be produced expressing human
cell II genes and human CD4 gene which will be used to generate a model
for AIDS. The lab will continue to serve as a resource for mouse strains,
embryo freezing and transgenic technology.
StatusFinished
Effective start/end date9/1/775/31/06

Funding

  • National Institutes of Health
  • National Institutes of Health: $352,750.00
  • National Institutes of Health
  • National Institutes of Health: $242,417.00
  • National Institutes of Health
  • National Institutes of Health: $352,750.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $352,750.00
  • National Institutes of Health: $217,546.00
  • National Institutes of Health: $245,809.00
  • National Institutes of Health
  • National Institutes of Health: $262,196.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $317,475.00
  • National Institutes of Health
  • National Institutes of Health: $352,750.00
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.