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Mob DNA. 2019 May 3;10:17. doi: 10.1186/s13100-019-0162-7. eCollection 2019.

Insertion of a chimeric retrotransposon sequence in mouse Axin1 locus causes metastable kinky tail phenotype.

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1Department of Physiology and Cell Biology, University of Nevada School of Medicine Center for Molecular Medicine, Room 207B 1664 North Virginia Street MS/0575, Reno, NV 89557 USA.
3Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007 USA.
2Avera McKennan Hospital and University Health Center, Sioux Falls, SD 57108 USA.
4Department of Obstetrics and Gynecology, University of Nevada, Reno School of Medicine, Reno, NV 89557 USA.
5Department of Biology, University of Nevada, Reno, Reno, NV 89557 USA.



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.


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.


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.


Alternative splicing; CRISPR/Cas9; DNA methylation; Epigenetic inheritance; Histone modification; IAP; LINE-1; MaLR; Retrotransposon

Conflict of interest statement

The animal use protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Nevada, Reno (protocol number 00494).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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