Inducible knock out of pregnancy-associated plasma protein-a gene expression in the adult mouse: Effect on vascular injury response

Cheryl A. Conover, Laurie K. Bale, David R. Powell

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) enhances local IGF signaling through its ability to proteolyze inhibitory IGF binding proteins. In vivo, PAPP-A (like IGF) appears to exhibit antagonistic pleiotropy; ie, it has beneficial effects early in life but detrimental effects later in life. Accordingly, PAPP-A knockout (KO) mice are born as proportional dwarfs and have diminished reproductive vigor and reduced peak bone mass acquisition at puberty. On the other hand, PAPP-A KO mice live approximately 30% longer than their wild-type littermates, with decreased incidence and severity of age-related diseases and resistance to adverse responses of vascular injury. To be able to distinguish the impact of PAPP-A deficiency in the adult from that in early life, we developed a mouse model suitable for inducible Cre recombinase-mediated excision of the PAPP-A gene. In this study, we characterize the conditional PAPP-AKOmouse model for efficacy of tamoxifen-induced floxed PAPP-A excision in various tissues of adult mice and demonstrate a significant (P=.0001) reduction of neointimal formation in these mice after unilateral carotid artery ligation.

Original languageEnglish (US)
Pages (from-to)2734-2738
Number of pages5
JournalEndocrinology
Volume154
Issue number8
DOIs
StatePublished - Aug 1 2013

ASJC Scopus subject areas

  • Endocrinology

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