title: Global deletion of Ankrd1 results in a wound-healing phenotype associated with dermal fibroblast dysfunction.
abstract: The expression of ankyrin repeat domain protein 1 (Ankrd1), a transcriptional cofactor and sarcomeric component, is strongly elevated by wounding and tissue injury. We developed a conditional Ankrd1(fl/fl) mouse, performed global deletion with Sox2-cre, and assessed the role of this protein in cutaneous wound healing. Although global deletion of Ankrd1 did not affect mouse viability or development, Ankrd1(-/-) mice had at least two significant wound-healing phenotypes: extensive necrosis of ischemic skin flaps, which was reversed by adenoviral expression of ANKRD1, and delayed excisional wound closure, which was characterized by decreased contraction and reduced granulation tissue thickness. Skin fibroblasts isolated from Ankrd1(-/-) mice did not spread or migrate on collagen- or fibronectin-coated surfaces as efficiently as fibroblasts isolated from Ankrd1(fl/fl) mice. More important, Ankrd1(-/-) fibroblasts failed to contract three-dimensional floating collagen gels. Reconstitution of ANKRD1 by adenoviral infection stimulated both collagen gel contraction and actin fiber organization. These in vitro data were consistent with in vivo wound closure studies, and suggest that ANKRD1 is important for the proper interaction of fibroblasts with a compliant collagenous matrix both in vitro and in vivo.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Samaras
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Karinna
authors.initials: K
authors.lastname: Almodóvar-García
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Nanjun
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee; Research Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee. Electronic address: jeff.davidson@vanderbilt.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Davidson
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry; D003433:Crosses, Genetic; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005782:Gels / Q000737:chemistry; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics*; D009336:Necrosis; D009687:Nuclear Proteins / Q000235:genetics*; D009929:Organ Size; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing
chemical_list: C104844:Ankrd1 protein, mouse; D005782:Gels; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins; D012313:RNA; D003094:Collagen