Data from: Fine mapping quanitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

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 nineteen 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 SNPs 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.

LG/J品系小鼠的外耳孔闭合可作为再生应答研究的模型。该过程伴随芽基样结构的形成，并实现包括软骨在内的多种组织再生。其组织再生能力具有可遗传性。为鉴定参与30天愈合周期中外耳孔闭合过程的基因组位点，研究人员构建了小鼠F34高级互交系（Wustl:LG,SM-G34）。本研究共定位得到19个与外耳孔闭合相关的定量性状位点（Quantitative Trait Locus, QTL）。单个基因的效应相对微弱（效应值为0.08 mm），且多数位点表现为共显性遗传效应，杂合子的表型处于中间状态。QTL支持区间的中位数长度为2 Mb，每个区间平均包含19个基因。研究人员通过比较LG/J与SM/J愈合组织的差异转录本表达、功能分析，以及对目标位置候选基因及其侧翼区域的单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）进行生物信息学分析，对位置候选基因进行了筛选验证。对34个位置候选基因及存在表达差异的基因进行富集分析后发现，这些基因显著富集于细胞周期调控/DNA损伤应答、细胞迁移与黏附、发育相关基因及代谢通路等功能类别。上述结果表明，LG/J小鼠的耳部愈合表型涉及多种生理调控机制。