Yu Hongrun, Baylink David J, Masinde Godfred L, Li Runzhi, Nguyen Bay, Davidson Heather M, Xu Shizhong, Mohan Subburaman
Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, California 92357, USA.
Wound Repair Regen. 2007 Nov-Dec;15(6):922-7. doi: 10.1111/j.1524-475X.2007.00317.x.
Development of gene therapies for wound healing will depend on the identification of the genes involved in wound healing and tissue regeneration. Previous quantitative trait loci (QTL) studies in mice using the ear punch model have shown that major QTL exist on chromosome (Chr) 9 for soft tissue regeneration. In this study, we have developed a congenic line that contains the Chr 9 QTL chromosomal region from super healer MRL/MpJ in the genomic background of poor-healing SJL/J. The phenotypic effect of this QTL was confirmed in male mice, where the congenic line has shown significant healing improvement over SJL. Fine mapping of the Chr 9 QTL region with 23 markers at an average distance of 4.2 Mb using a total of 1,564 MRL/MpJ x SJL/J F(2) mice revealed the presence of at least three QTL peaks, implying that three separate loci may contribute to the phenotypic effect of this QTL. Based on the 2-LOD intervals, the total QTL region was confined to a combined length of no more than 28.2 Mb. Application of a Bayesian shrinkage estimation indicated that a major locus was located in a region of just 1.3 Mb.
伤口愈合基因疗法的发展将取决于对参与伤口愈合和组织再生的基因的识别。此前使用打孔模型对小鼠进行的数量性状基因座（QTL）研究表明，9号染色体（Chr）上存在影响软组织再生的主要QTL。在本研究中，我们培育了一个近交系，其在愈合能力较差的SJL/J基因组背景中包含来自超级愈合品系MRL/MpJ的9号染色体QTL染色体区域。该QTL在雄性小鼠中的表型效应得到了证实，其中该近交系显示出比SJL显著更好的愈合效果。使用总共1564只MRL/MpJ×SJL/J F(2)小鼠，用平均间距为4.2 Mb的23个标记对9号染色体QTL区域进行精细定位，结果显示至少存在三个QTL峰值，这意味着三个独立的基因座可能对该QTL的表型效应有贡献。基于2-LOD区间，总的QTL区域被限定在不超过28.2 Mb的组合长度内。贝叶斯收缩估计的应用表明，一个主要基因座位于仅1.3 Mb的区域内。
