Hormonal modulation of a gene injected into rat heart in vivo

R. N. Kitsis, P. M. Buttrick, E. M. McNally, M. L. Kaplan, L. A. Leinwand

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

We demonstrate gene transfer into rat heart in vivo by the direct injection of plasmid DNA. Injection of gene constructs driven by retroviral and cellular promoters resulted in detectable levels of reporter gene activities. The cellular promoter and 5' flanking sequence (positions -613 to +32) were derived from the rat α-myosin heavy chain gene whose expression in vivo is restricted to cardiac muscle and is positively regulated by thyroid hormone. After DNA injection, activity of the firefly luciferase gene coupled to the myosin heavy chain promoter and regulatory sequence was detected in heart but not in skeletal muscle and was significantly increased in response to thyroid hormone treatment. Consequently, expression of injected genes can be targeted to specific cell types in vivo and can be modulated by the hormonal status of the animal. This approach provides a means of mapping the elements of genes that regulate their responses to complex stimuli that cannot be modeled in vitro.

Original languageEnglish (US)
Pages (from-to)4138-4142
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number10
DOIs
StatePublished - Jan 1 1991

Keywords

  • cardiac gene transfer
  • gene regulation
  • myosin heavy chain
  • thyroid hormone
  • transfection

ASJC Scopus subject areas

  • General

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