A transgenic mouse model for the simultaneous monitoring of ANF and BNP gene activity during heart development and disease

Cardiovasc Res. 2014 Jan 1;101(1):78-86. doi: 10.1093/cvr/cvt228. Epub 2013 Oct 8.


Aim: The expression of Nppa (ANF) and Nppb (BNP) marks the chamber myocardium in the embryo, and both genes serve as early and accurate markers for hypertrophy and heart failure. Non-invasive visualization of Nppa-Nppb expression in living mice would enable to evaluate the disease state during the course of time in heart disease models. We sought to develop a method to assess the pattern and level of Nppa and Nppb expression within living mice.

Methods and results: A modified bacterial artificial chromosome containing a genomic segment spanning the Nppa-Nppb locus was randomly integrated into the mouse genome. Firefly Luciferase was inserted into Nppa and the red fluorescent protein gene Katushka into Nppb. Both reporters precisely recapitulated the spatio-temporal patterns of Nppa and Nppb, respectively. In a hypertrophy model (transverse aortic constriction) and myocardial infarction model (left anterior descending coronary artery occlusion), the non-invasively measured bioluminescent signal from Luciferase correlated with Nppa expression, and the intensity of red fluorescence with levels of the expression of Katushka and Nppb. After myocardial infarction, the border zone of the infarct area was readily identified by an increased intensity of Katushka fluorescence.

Conclusions: A genomic region sufficient to regulate the developmental pattern and stress response of Nppa and Nppb has been defined. The double reporter mice can be used for the functional imaging and investigation of cardiac hypertrophy and myocardial infarction in vivo.

Keywords: Bioluminescent imaging; Double reporter; Hypertrophy; Myocardial infarction; Natriuretic peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / metabolism*
  • Cardiomegaly / metabolism*
  • Chromosomes, Artificial, Bacterial
  • Disease Models, Animal
  • Genes, Reporter*
  • Heart Ventricles / metabolism
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Myocardial Infarction / metabolism*
  • Natriuretic Peptide, Brain / metabolism*
  • Up-Regulation


  • Luminescent Proteins
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor