Skip to main content
Journal cover image

Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.

Publication ,  Journal Article
Rockman, HA; Ross, RS; Harris, AN; Knowlton, KU; Steinhelper, ME; Field, LJ; Ross, J; Chien, KR
Published in: Proc Natl Acad Sci U S A
September 15, 1991

To study the mechanisms that activate expression of the atrial natriuretic factor (ANF) gene during pressure-induced hypertrophy, we have developed and characterized an in vivo murine model of myocardial cell hypertrophy. We employed microsurgical techniques to produce a stable 35- to 45-mmHg pressure gradient across the thoracic aorta of the mouse that is associated with rapid and transient expression of an immediate-early gene program (c-fos/c-jun/junB/Egr-1/nur-77), an increase in heart weight/body weight ratio, and up-regulation of the endogenous ANF gene. These responses that are identical to those in cultured cell and other in vivo models of hypertrophy. To determine whether tissue-specific and inducible expression of the ANF gene can be segregated, we used a transgenic mouse line in which 500 base pairs of the human ANF promoter region directs atrial-specific expression of the simian virus 40 large tumor antigen (T antigen), with no detectable expression in the ventricles. Thoracic aortic banding of these mice led to a 20-fold increase in the endogenous ANF mRNA in the ventricle but no detectable expression of the T-antigen marker gene. This result provides evidence that atrial-specific and inducible expression of the ANF gene can be segregated, suggesting that a distinct set of regulatory cis sequences may mediate the up-regulation of the ANF gene during in vivo pressure overload hypertrophy. This murine model demonstrates the utility of microsurgical techniques to study in vivo cardiac physiology in transgenic mice and should allow the application of genetic approaches to identify the mechanisms that activate ventricular expression of the ANF gene during in vivo hypertrophy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 15, 1991

Volume

88

Issue

18

Start / End Page

8277 / 8281

Location

United States

Related Subject Headings

  • Transcription Factors
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Mice, Transgenic
  • Mice
  • Immediate-Early Proteins
  • Hypertension
  • Hemodynamics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rockman, H. A., Ross, R. S., Harris, A. N., Knowlton, K. U., Steinhelper, M. E., Field, L. J., … Chien, K. R. (1991). Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci U S A, 88(18), 8277–8281. https://doi.org/10.1073/pnas.88.18.8277
Rockman, H. A., R. S. Ross, A. N. Harris, K. U. Knowlton, M. E. Steinhelper, L. J. Field, J. Ross, and K. R. Chien. “Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.Proc Natl Acad Sci U S A 88, no. 18 (September 15, 1991): 8277–81. https://doi.org/10.1073/pnas.88.18.8277.
Rockman HA, Ross RS, Harris AN, Knowlton KU, Steinhelper ME, Field LJ, et al. Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8277–81.
Rockman, H. A., et al. “Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.Proc Natl Acad Sci U S A, vol. 88, no. 18, Sept. 1991, pp. 8277–81. Pubmed, doi:10.1073/pnas.88.18.8277.
Rockman HA, Ross RS, Harris AN, Knowlton KU, Steinhelper ME, Field LJ, Ross J, Chien KR. Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8277–8281.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 15, 1991

Volume

88

Issue

18

Start / End Page

8277 / 8281

Location

United States

Related Subject Headings

  • Transcription Factors
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Mice, Transgenic
  • Mice
  • Immediate-Early Proteins
  • Hypertension
  • Hemodynamics