title: Inducible knock out of pregnancy-associated plasma protein-a gene expression in the adult mouse: effect on vascular injury response.
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-A KO mouse 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.
authors.affiliation: The Endocrine Research Unit, Division of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA. conover.cheryl@mayo.edu
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Conover
authors.forename: Laurie K
authors.initials: LK
authors.lastname: Bale
authors.forename: David R
authors.initials: DR
authors.lastname: Powell
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D008026:Ligation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000172:deficiency* / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D050071:Bone Density Conservation Agents; D013629:Tamoxifen; D011266:Pregnancy-Associated Plasma Protein-A