Project: Research project

Project Details


Techniques currently exist which permit the introduction of recombinant DNA
molecules into the mouse germline, thereby creating "transgenic" lineages
which carry the integrated DNA as a stable, heritable trait. Moreover, the
techniques provide a means with which to correlate defined genetic
alterations of the integrated "transgene" with their resultant
physiological consequences in intact animals. In this study, the
relationship between aberrant Atrial Natriuretic Factor (ANF) expression
and hypertension will be investigated. ANF is a peptide hormone produced
by the heart which exhibits potent natriuretic and hypotensive properties,
and which appears to play a crucial role in the regulation of blood
pressure and electrolyte homeostasis. Transgenic lineages will be
generated which carry defined alterations of the human ANF gene. Molecular
and physiological analyses will be performed on the various lineages to
determine the effect of transgene expression on both blood pressure and
electrolyte balance. In addition, the physiological response of other
components of the blood pressure regulatory cascade will be determined (for
example, renin, angiotensin and aldosterone). Initially three experimental
tacts will be pursued. They are: 1) experiments which will define the
human ANF promoter. 2) experiments which will define the physiological
consequences of aberrant ANF regulation due to oncogene expression in
atrial pericardiocytes. 3) experiments which will define the physiological
consequences of ANF expression directed by heterologous promoters. The
proposed experiments will address interesting questions pertaining to the
regulation of the ANF gene, as well as provide a model system in which to
study the relationship between aberrant ANF expression and hypertension.
Effective start/end date4/1/873/31/92


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $59,931.00
  • National Institutes of Health


  • Medicine(all)


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