GENE INTRODUCTION AND EXPRESSION IN THE DEVELOPING MOUSE

Project Details

Description

A molecular-genetic approach is required to fully understand the complex
developmental and physiological processes that occur within a mammalian
organism. The mutation at the mouse pygmy locus leads to a disruption of
the overall pattern of growth and development and gives rise to mice that
are miniature in size. The aim of this proposal is to continue and expand
the studies on the pygmy locus which has been cloned via insertional
mutagenesis in transgenic mice.

The experimental approach will be to further characterize this mutation at
the phenotypic and molecular level. A detailed histological analysis of
the hypothalamus, pituitary, thyroid and adrenal will be carried out since
this axis seems to be perturbed in the mutants. The hormone levels
secreted by these tissues and those involved in growth will also be
thoroughly investigated. The initial aim of the molecular biology
experiments will be to isolate the pygmy gene product. This will be
achieved by cloning the normal locus and isolating conserved single copy
sequences between different species. These sequences will then by
hybridized with RNa isolated from embryos at various developmental stages
and different adult tissues. A cDNA library will be constructed form the
appropriate expressing tissue and the whole coding region isolated,
sequenced and used to investigate the developmental and tissue specific
expression of the gene. The protein will be overexpressed in E. coli and
antibodies generated to elucidate the cellular localization of the protein.

Gene therapy and gene disruption experiments will prove unequivocally if
the isolated gene is actually responsible for the dwarf phenotype.
Finally, the homologous gene from humans will be isolated and used to see
if there s a mutation in families suffering from non growth hormone-
deficient dwarf syndromes.

The eventual aim of these studies is to attempt to understand the
physiological role of the pygmy gene product in growth and development. In
addition, these investigations will determine the utility of the mutant
mice as molecularly authentic murine analogs of non growth hormone-
deficient human dwarf syndromes.
StatusFinished
Effective start/end date1/1/906/30/96

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

  • Genetics
  • Molecular Biology

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