Insertion of a chimeric retrotransposon sequence in mouse Axin1 locus causes metastable kinky tail phenotype
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Authors
Wang, Zhuqing
McSwiggin, Hayden
Newkirk, Simon J.
Wang, Yue
Oliver, Daniel K.
Tang, Chong
Lee, Sandy
Wang, Shawn
Yuan, Shuiqiao
Zheng, Huili
Issue Date
2019
Type
Article
Language
Keywords
Retrotransposon , CRISPR/Cas9 , LINE-1 , IAP , MaLR , Alternative splicing , Histone modification , DNA methylation , Epigenetic inheritance
Alternative Title
Abstract
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.ResultsWe 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 similar to 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 (similar to 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.ConclusionsThe 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.
Description
Citation
Wang, Z., McSwiggin, H., Newkirk, S. J., Wang, Y., Oliver, D., Tang, C., É Yan, W. (2019). Insertion of a chimeric retrotransposon sequence in mouse Axin1 locus causes metastable kinky tail phenotype. Mobile DNA, 10(1). doi:10.1186/s13100-019-0162-7
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Journal
Volume
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PubMed ID
ISSN
1759-8753