Key Points
- To determine whether a 2.4-kilobase regulatory region of the rat atrial natriuretic factor gene directs tissue-specific and developmentally regulated expression in a mouse model.
- Generated transgenic mice carrying 2.4 kilobases of the rat atrial natriuretic factor gene regulatory region coupled to a chloramphenicol acetyltransferase reporter.
- Assayed reporter enzyme activity in adult cardiac and non-cardiac tissues, including the atria, ventricles, and hypothalamus.
- Evaluated developmental expression profiles in fetal and neonatal tissues and compared them to endogenous murine atrial natriuretic factor gene expression.
- The 2.4-kilobase regulatory sequence directed 4000-fold higher chloramphenicol acetyltransferase expression in adult atria than in ventricles, with low-level activity also detected in the hypothalamus.
- Transgene expression was elevated in both fetal atria and ventricles but exhibited a steep reduction in ventricular tissue after birth.
- The developmental expression profile of the transgene mirrored that of the neonatal rat rather than the endogenous mouse atrial natriuretic factor gene.
Structured PICO
PPopulationTransgenic mice
IInterventionExpression of prokaryotic marker protein chloramphenicol acetyltransferase under the control of 2.4 kilobases of the rat atrial natriuretic factor gene regulatory region
CComparatorEndogenous murine atrial natriuretic factor gene
OOutcomeTissue specificity and developmental regulation of transgene expressionsurrogate
The 2.4-kilobase regulatory sequence of the rat atrial natriuretic factor gene contains cis-acting signals that dominantly control correct tissue specificity and developmental regulation in transgenic mice.