title: Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line.
abstract: External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage. The ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Cheverud
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Lawson
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bouckaert
authors.affiliation: Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Kossenkov
authors.affiliation: Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Showe
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Cort
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Blankenhorn
authors.affiliation: Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bedelbaeva
authors.affiliation: Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gourevitch
authors.affiliation: Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Heber-Katz
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003433:Crosses, Genetic; D004431:Ear, External / Q000502:physiology*; D005838:Genotype; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012038:Regeneration / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C541430:MKLP1 protein, mouse; D016547:Kinesins