Hoxa5/Cre transgenic mice: novel tools for regional deletion along the anterior-posterior axis

Abstract

The Hoxa5 homeobox gene encodes a transcription factor that plays a critical role in specifying the identity of the cervico-thoracic region along the anterior-posterior embryo axis and in orchestrating organ morphogenesis. The loss of Hoxa5 function results in skeletal transformations, lethality at birth due to lung defects, and organ anomalies affecting the digestive tract, the mammary gland and the ovary. Study of Hoxa5 gene regulation has revealed the interplay of several control regions that direct Hoxa5 developmental expression. Enhancers targeting expression in the CNS, the paraxial and lateral plate mesoderm at the cervico-thoracic level, and in the mesenchymal compartment of the respiratory and digestive tracts have been identified. Using these molecular tools, we have generated two Hoxa5/Cre transgenic mouse lines carrying different combinations of Hoxa5 regulatory enhancers and allowing site-specific recombination in subsets of Hoxa5 expression sites as tested with the Rosa26/lacZ reporter mice. Further validation of the recombination efficiency of the Hoxa5/Cre transgenic lines was performed with mice carrying a Hoxa5 conditional allele. Hoxa5 deletion with the Hoxa5/Cre mouse lines recapitulates Hoxa5 mutant phenotypes, such as skeletal defects, neonatal lethality, and lung malformations. Hoxa5/Cre mouse lines provide novel genetic tools for gene function analysis in defined tissues along the anterior-posterior axis.

Keywords: Cre recombinase; Hoxa5; anterior-posterior axis; lung and gut morphogenesis.