Yu Hongrun, Mohan Subburaman, Masinde Godfred L, Baylink David J
Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, California 92357, USA.
Mamm Genome. 2005 Dec;16(12):918-24. doi: 10.1007/s00335-005-0077-0. Epub 2005 Dec 8.
We have used a mouse ear punch model and the QTL (quantitative trait loci) mapping technique to identify genes that are responsible for soft tissue regeneration. In the early studies, we have identified several QTL and have shown that the inheritance of ear healing was additive in one cross (MRL x SJL), and recessive in another cross (DBA x 129). Because CAST mice are genetically distinct and have a different genetic background, CAST would facilitate the identification of common and novel QTL when crossed with common inbred lines. We made a cross between super healer MRL and poor healer CAST and collected ear punch phenotype and marker genotype data from F(2). Ear punch healing exhibited a dominant mode of inheritance in this cross. There were three main QTL on Chromosomes 4, 9, and 17, and two suggestive QTL on Chromosomes 1 (new) and 7. Taken together, these QTL accounted for about 29% of total F2 variance of MRL x CAST. Compared with another study using the same cross, we found a totally different set of QTL. Two QTL interactions were identified by a full QTL model: Chromosomes 4 x 17 and 9 x 17; the latter reached to a statistical level at p < 0.05. These interactions explained about 4% of the F2 phenotypic variance. We conclude that soft tissue regeneration is controlled by multiple genes and locus vs. locus interactions.
我们使用了小鼠耳打孔模型和QTL（数量性状位点）定位技术来鉴定负责软组织再生的基因。在早期研究中，我们已经鉴定出了几个QTL，并表明耳部愈合的遗传在一个杂交组合（MRL×SJL）中是加性的，而在另一个杂交组合（DBA×129）中是隐性的。由于CAST小鼠在基因上是独特的，具有不同的遗传背景，与常见近交系杂交时，CAST将有助于鉴定常见和新的QTL。我们将超级愈合者MRL与愈合不良者CAST进行杂交，并从F2代收集耳打孔表型和标记基因型数据。在这个杂交组合中，耳打孔愈合表现出显性遗传模式。在4号、9号和17号染色体上有三个主要的QTL，在1号（新的）和7号染色体上有两个暗示性的QTL。这些QTL加起来约占MRL×CAST总F2变异的29%。与另一项使用相同杂交组合的研究相比，我们发现了一组完全不同的QTL。通过完整的QTL模型鉴定出两个QTL相互作用：4号染色体×17号染色体和9号染色体×17号染色体；后者在p<0.05时达到统计学水平。这些相互作用解释了约4%的F2表型变异。我们得出结论，软组织再生受多个基因以及位点与位点之间相互作用的控制。
