Genetic loss of proadrenomedullin N-terminal 20 peptide (PAMP) in mice is compatible with survival

Abstract

Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are small peptides derived from a common precursor, pre-proadrenomedullin. Although AM and PAMP share hypotensive effects in the cardiovascular system, the peptides also exert diverse and distinct effects on endocrine physiology, innate immunity, cytoskeletal biology and receptor signaling pathways. Tremendous knowledge has been gleaned from the study of several genetic animal models of AM deletion or overexpression, some of which also simultaneously delete the coding region for PAMP peptide. However, deletion of PAMP without concurrent deletion of AM in an animal model is not currently available for the study of PAMP function. Here, we present the generation of AdmΔPAMP/ΔPAMP and AdmΔPAMP/− mice, which lack the coding sequence for PAMP while preserving the coding sequence for AM. AdmΔPAMP/ΔPAMP mice survive to adulthood without any obvious abnormalities and are fertile, though AdmΔPAMP/− females have small litters. Interestingly, these animals express lower levels of Adm mRNA and AM peptide than wild type animals, but these levels are still compatible with survival. Importantly, despite reduced levels, the spatiotemporal expression of AM peptide within the hearts of AdmΔPAMP/− mice remains similar to wild type animals. AdmΔPAMP/ΔPAMP mice are now a publicly available tool for future investigations of PAMP function.