ArticleGenome research2019
Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis.
Article in Genome research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed, 219 citations in OpenAlex.
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- Methylomic signatures of tau and amyloid-beta in transgenic mouse models of Alzheimer's disease neuropathology.NPJ dementia · 2026Article
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- Boosting angiotensin-converting enzyme (ACE) in microglia protects against Alzheimer's disease in 5xFAD mice.Nature aging · 2025Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Transgenesis has been a mainstay of mouse genetics for over 30 yr, providing numerous models of human disease and critical genetic tools in widespread use today. Generated through the random integration of DNA fragments into the host genome, transgenesis can lead to insertional mutagenesis if a coding gene or an essential element is disrupted, and there is evidence that larger scale structural variation can accompany the integration. The insertion sites of only a tiny fraction of the thousands of transgenic lines in existence have been discovered and reported, due in part to limitations in the discovery tools. Targeted locus amplification (TLA) provides a robust and efficient means to identify both the insertion site and content of transgenes through deep sequencing of genomic loci linked to specific known transgene cassettes. Here, we report the first large-scale analysis of transgene insertion sites from 40 highly used transgenic mouse lines. We show that the transgenes disrupt the coding sequence of endogenous genes in half of the lines, frequently involving large deletions and/or structural variations at the insertion site. Furthermore, we identify a number of unexpected sequences in some of the transgenes, including undocumented cassettes and contaminating DNA fragments. We demonstrate that these transgene insertions can have phenotypic consequences, which could confound certain experiments, emphasizing the need for careful attention to control strategies. Together, these data show that transgenic alleles display a high rate of potentially confounding genetic events and highlight the need for careful characterization of each line to assure interpretable and reproducible experiments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.