McBrearty B A, Clark L D, Zhang X M, Blankenhorn E P, Heber-Katz E
Wistar Institute, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11792-7. doi: 10.1073/pnas.95.20.11792.
Wound healing of mammalian tissue is an essential process in the maintenance of body integrity. The general mechanism of wound healing usually studied in adult mammals is repair, in contrast to the regeneration seen in more primitive vertebrates. We recently have discovered that MRL/MpJ mice, unlike all other strains of mice tested, undergo rapid and complete wound closure that resembles regeneration. Specifically, through-and-through surgical ear hole wounds close without scarring in <4 weeks with normal gross and microanatomic architecture, including chondrogenesis. We also demonstrated that this healing is a heritable trait in inbred mice. In this study, we present results pertaining to its genetic control in progeny segregating for this phenotype. To identify the genetic loci that control the wound closure process, a genome-wide scan was performed on (MRL/MpJ-Faslpr x C57BL/6)F2 and backcross populations. In the primary screens of these populations, quantitative trait loci that control the extent of wound closure were detected on chromosomes 8, 12, and 15 and at two separate locations on chromosome 13. Evidence of further genetic control of healing was found on chromosome 7. All alleles that contribute to full wound closure are derived from the MRL/MpJ-Faslpr parent except for the quantitative trait locus on chromosome 8, which is derived from C57BL/6.
哺乳动物组织的伤口愈合是维持身体完整性的一个重要过程。与在更原始的脊椎动物中看到的再生不同，通常在成年哺乳动物中研究的伤口愈合的一般机制是修复。我们最近发现，与所有其他测试过的小鼠品系不同，MRL/MpJ小鼠能够快速且完全地闭合伤口，这类似于再生。具体而言，贯通性手术造成的耳洞伤口在不到4周的时间内即可闭合，且无疤痕形成，其大体和微观解剖结构正常，包括软骨形成。我们还证明，这种愈合是近交系小鼠的一种可遗传性状。在本研究中，我们展示了在为该表型分离的后代中其遗传控制的相关结果。为了确定控制伤口闭合过程的基因座，对（MRL/MpJ-Faslpr×C57BL/6）F2和回交群体进行了全基因组扫描。在这些群体的初步筛选中，在8号、12号和15号染色体以及13号染色体上的两个不同位置检测到了控制伤口闭合程度的数量性状基因座。在7号染色体上发现了愈合过程进一步受到遗传控制的证据。除了8号染色体上的数量性状基因座来自C57BL/6外，所有有助于伤口完全闭合的等位基因均来自MRL/MpJ-Faslpr亲本。
