INTRODUCTION/EXPRESSION OF GENES

Project Details

Description

The initial set of proposed experiments is an attempt to
understand the genetic mechanisms that control the sequential
utilization of different globin genes during mammalian
development, the phenemenon known as hemoglobin switching.
The globin genes provide an excellent opportunity to examine the
question of developmental regualation of gene expression because
they have been intensively characterized with respect to their
structure and expression. Insights into the developmental
regulation of globin genes are of clinical significance because of
the many hereditary disease associated with anomalous
hemoglobin synthesis in man. The experimental approach to this problem involves the
introduction of cloned beta globin genes into the germline of
mice. The expression pattern of these genes will be analyzed in
the transgenic mice and their mice and their progeny at the RNA
and protein level in the various erythroid tissues during ontogeny.
There are three extremely homolgous (greater than 90%) beta
globin genes in goats which are descended from a common
ancestral adult beta globin gene and yet they have a differential
pattern of expression. Transgenic mouse lines will be generated
that contain each of these beta globin genes and the expression
pattern examined. From these results, hybrid genes containing
portions of two different genes will be constructed and tested for
expression in order to delineate what sequences play a role in the
switching process. In the second project, experiments will also be performed to
isolate developmental mutants which have arisen due to the
insertion of foreign DNA into the mouse genome. The third
project will attempt to develop a method for the elimination of B
lymphocytes within the mouse. This will be carried out by
introducing, into mouse eggs, a DNA fragment containing the
immunoglobulin regulatory sequences which confer cell-specific
expression linked to a gene whose product should kill the cell.
This transgenic mouse could be used as a model system for a
disease, agammaglobulinemia, in humans characterized by the
inability to produce gammaglobulin. If generalized, this method
could be used to make other murine analogs of human disease as
well as to observe the phenotypic effects that resulted from the
absence of a particular cell type.
StatusFinished
Effective start/end date12/31/896/30/96

Funding

  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Genetics
  • Molecular Biology

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