Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

Heredity (Edinb). 2014 May;112(5):508-18. doi: 10.1038/hdy.2013.133. Epub 2014 Feb 26.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping / methods*
  • Crosses, Genetic
  • Ear, External / physiology*
  • Genotype
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Kinesin / genetics
  • Kinesin / metabolism
  • Mice
  • Mice, Inbred Strains
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci / genetics*
  • Regeneration / genetics*
  • Transcriptome / genetics
  • Wnt3A Protein / genetics
  • Wnt3A Protein / metabolism
  • Wound Healing / genetics

Substances

  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • MKLP1 protein, mouse
  • Kinesin