Project Details

Description

The extracellular matrix (ECM) is essential for the integrity of all
tissues. Its importance can easily be realized when the connective tissue
in the lung is destroyed which then leads to emphysema. However, progress
in the treatment of this disease has been slow because the etiology of the
major forms of emphysema remain unresolved. Also, the available animal
models do not mimic the human disease in many important respects. The aim
of this proposal is to study a transgenic mouse model which suggests a new
etiological agent, collagenase, in emphysema. The experimental approach is to further characterize these transgenic mice
which express collagenase in the lung and suffer from emphysema. First,
the specificity of transgene expression in different tissues will be
examined by RNAse protection analysis. In situ hybridization will
identify the cell type expressing the transgene. Next, the temporal
regulation of transgene expression will be defined at various
developmental stages. The expression levels of genes which may be
perturbed by collagenase overexpression will be analyzed so as to define
the overall regulation of lung ECM synthesis. The transgene will be bred
on various genetic backgrounds to identify loci which modify the emphysema
phenotype. To assess the utility of these mice as human disease models, a
detailed histological analysis of the lungs with the electron microscope
will be performed and the mice observed for secondary symptoms that arise
from prolonged emphysema. The eventual aim of these studies is to understand the pathogenesis of
emphysema and provide a defined animal model to follow the pathophysiology
of the disease. This model could be used to examine therapeutic methods in
preventing the development of emphysema which is only second to heart
disease in contributing to major disability in the USA.
StatusFinished
Effective start/end date4/1/943/31/98

Funding

  • National Institutes of Health: $285,072.00
  • National Institutes of Health
  • National Institutes of Health: $229,508.00

ASJC

  • Medicine(all)

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