BACKGROUND Transposable elements (TEs) make up > 50% of the human genome, and the majority of retrotransposon insertions are truncated and many are located in introns. However, the effects of retrotransposition on the host genes remain incompletely known. RESULTS We report here that insertion of a chimeric L1 (cL1), but not IAP solo LTR, into intron 6 of Axin1 using CRIPSR/Cas9 induced the kinky tail phenotype with ~ 80% penetrance in heterozygous Axin cL1 mice. Both penetrant (with kinky tails) and silent (without kinky tails) Axin cL1 mice, regardless of sex, could transmit the phenotype to subsequent generations with similar penetrance (~ 80%). Further analyses revealed that a longer Axin1 transcript isoform containing partial cL1-targeted intron was present in penetrant, but absent in silent and wild type mice, and the production of this unique Axin1 transcript appeared to correlate with altered levels of an activating histone modification, H3K9ac. CONCLUSIONS The mechanism for Axin cL1 mice is different from those previously identified in mice with spontaneous retrotransposition of IAP, e.g., Axin Fu and A vy , both of which have been associated with DNA methylation changes. Our data suggest that Axin1 locus is sensitive to genetic and epigenetic alteration by retrotransposons and thus, ideally suited for studying the effects of new retrotransposition events on target gene function in mice.

中文翻译：

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在小鼠 Axin1 基因座中插入嵌合反转录转座子序列会导致亚稳态扭结尾表型。

背景转座子元件（TE）占人类基因组的> 50％，并且大部分反转录转座子插入被截短并且许多位于内含子中。然而，逆转录转座对宿主基因的影响仍不完全清楚。结果 我们在此报告使用 CRIPSR/Cas9 将嵌合 L1 (cL1) 而不是 IAP 单独 LTR 插入 Axin1 的内含子 6，在杂合 Axin cL1 小鼠中诱导了具有约 80% 外显率的扭尾表型。无论性别如何，外显型（带有弯曲的尾巴）和沉默型（没有弯曲的尾巴）的 Axin cL1 小鼠都可以将表型传递给具有相似外显率（~ 80%）的后代。进一步的分析表明，含有部分 cL1 靶向内含子的较长 Axin1 转录亚型存在于渗透剂中，但在沉默型和野生型小鼠中不存在，并且这种独特的 Axin1 转录物的产生似乎与激活组蛋白修饰 H3K9ac 水平的改变相关。结论 Axin cL1 小鼠的机制不同于先前在 IAP 自发性逆转录转座小鼠中发现的机制，例如 Axin Fu 和 A vy，两者都与 DNA 甲基化变化有关。我们的数据表明 Axin1 基因座对反转录转座子的遗传和表观遗传改变敏感，因此非常适合研究新的反转录转座事件对小鼠靶基因功能的影响。Axin Fu 和 A vy 都与 DNA 甲基化变化有关。我们的数据表明 Axin1 基因座对反转录转座子的遗传和表观遗传改变敏感，因此非常适合研究新的反转录转座事件对小鼠靶基因功能的影响。Axin Fu 和 A vy 都与 DNA 甲基化变化有关。我们的数据表明 Axin1 基因座对反转录转座子的遗传和表观遗传改变敏感，因此非常适合研究新的反转录转座事件对小鼠靶基因功能的影响。