title: Mapping Novel Subcutaneous Angiogenesis Quantitative Trait Loci in [B6×MRL]F2 Mice.
abstract: Objective:MRL/MpJ mice are known for enhanced healing, but mechanistic details or how specific aspects of wounding (e.g., angiogenesis) contribute to healing are unknown. While previous studies investigated the systemic effects of immunity in MRL/MpJ healing, few have focused on tissue-intrinsic effects.Approach:Ex vivoskin biopsies from MRL/MpJ and C57BL/6J mice were cultured inex vivoconditions that favor endothelial cell growth to compare their angiogenic potential. We localized enhanced angiogenesis quantitative trait loci (QTL) in an F2 intercross. We then performed an expression analysis in cultured skin biopsies from MRL/MpJ and C57BL/6J mice to determine the pathways that are associated with the capacity for differential growth.Results:MRL/MpJ biopsies have a two- to threefold greater growth potential than C57BL/6J mice, supporting the hypothesis that angiogenesis may contribute to enhanced healing in MRL/MpJ skin. We mapped two QTLs that are unique from previously mapped MRL/MpJ wound healing QTLs and detected interactions between wound healing QTLs and loci in this cross. Additionally, we found that pathways previously implicated in MRL/MpJ healing are also enriched in skin biopsies.Innovation:We have developed a novel approach to determine how specific aspects of tissue development contribute to wound healing that will ultimately lead to the discovery of unidentified genes that contribute to enhanced healing.Conclusion:We have shown that, consistent with previous studies following wound closure in MRL/MpJ mice, vessel growth during healing is also influenced by genetic background. Our ongoing work will identify the genetic factors that should be useful biomarkers or as therapeutic targets for enhanced wound healing.
authors.affiliation: Wadsworth Center , NYS Department of Health, Albany, New York.
authors.forename: Krista
authors.initials: K
authors.lastname: Morales
authors.affiliation: Forensic Biology, State University of New York at Albany , Albany, New York.
authors.forename: Leahana
authors.initials: L
authors.lastname: Rowehl
authors.affiliation: Wadsworth Center , NYS Department of Health, Albany, New York.
authors.forename: Jason
authors.initials: J
authors.lastname: Smith
authors.affiliation: Wadsworth Center , NYS Department of Health, Albany, New York. ; School of Public Health, State University of New York at Albany , Albany, New York.
authors.forename: Rich
authors.initials: R
authors.lastname: Cole
authors.affiliation: School of Public Health, State University of New York at Albany , Albany, New York.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Wadsworth Center , NYS Department of Health, Albany, New York.
authors.forename: Barb
authors.initials: B
authors.lastname: Beyer
authors.affiliation: Wadsworth Center , NYS Department of Health, Albany, New York. ; School of Public Health, State University of New York at Albany , Albany, New York.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Herron