ArticleCell & bioscience2021
When the genome bluffs: a tandem duplication event during generation of a novel Agmo knockout mouse model fools routine genotyping.
Article in Cell & bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Utilization of long-read sequencing for the detection of structural rearrangements with AgileStructure.Bioinformatics (Oxford, England) · 2026Article
- Make or break - PEDS1 and AGMO orchestrate ether lipid homeostasis in human adipocytes and are associated with blood lipid profiles.Journal of translational medicine · 2026Observational
- Alkylglycerol monooxygenase represses prostanoid biosynthesis in a sex-dependent manner.Cell & bioscience · 2025Article
- Transgene Mapping in Animals: What to Choose?International journal of molecular sciences · 2025Review
- Long read sequencing reveals transgene concatemerization and vector sequences integration following AAV-driven electroporation of CRISPR RNP complexes in mouse zygotes.Frontiers in genome editing · 2025Article
- Genome editing in East African cichlids and tilapias: state-of-the-art and future directions.Open biology · 2023Review
- CRISPR-Cas9 Long-Read Sequencing for Mapping Transgenes in the Mouse Genome.The CRISPR journal · 2023Article
- Increased On-Target Rate and Risk of Concatemerization after CRISPR-Enhanced Targeting in ES Cells.Genes · 2023Article
- NEAT1 variant 1 weakens the genome-wide effect of miR-3122 on blocking H3K79me3 in bladder cancer.Aging · 2022Article
- Adaptations of the 3T3-L1 adipocyte lipidome to defective ether lipid catabolism upon Agmo knockdown.Journal of lipid research · 2022Article
- Importing genetically altered animals: ensuring quality.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- Regulation of plasmalogen metabolism and traffic in mammals: The fog begins to lift.Frontiers in cell and developmental biology · 2022Review
- Impact of Automated Genotyping and Increased Breeding Oversight on Overall Mouse Breeding Colony Productivity.Frontiers in physiology · 2022Article
- Review
- AGMO Inhibitor Reduces 3T3-L1 Adipogenesis.Cells · 2021Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundGenome editing in mice using either classical approaches like homologous recombination or CRISPR/Cas9 has been reported to harbor off target effects (insertion/deletion, frame shifts or gene segment duplications) that lead to mutations not only in close proximity to the target site but also outside. Only the genomes of few engineered mouse strains have been sequenced. Since the role of the ether-lipid cleaving enzyme alkylglycerol monooxygenase (AGMO) in physiology and pathophysiology remains enigmatic, we created a knockout mouse model for AGMO using EUCOMM stem cells but unforeseen genotyping issues that did not agree with Mendelian distribution and enzyme activity data prompted an in-depth genomic validation of the mouse model.
resultsWe report a gene segment tandem duplication event that occurred during the generation of an Agmo knockout-first allele by homologous recombination. Only low homology was seen between the breakpoints. While a single copy of the recombinant 18 kb cassette was integrated correctly around exon 2 of the Agmo gene, whole genome nanopore sequencing revealed a 94 kb duplication in the Agmo locus that contains Agmo wild-type exons 1-3. The duplication fooled genotyping by routine PCR, but could be resolved using qPCR-based genotyping, targeted locus amplification sequencing and nanopore sequencing. Despite this event, this Agmo knockout mouse model lacks AGMO enzyme activity and can therefore be used to study its physiological role.
conclusionsA duplication event occurred at the exact locus of the homologous recombination and was not detected by conventional quality control filters such as FISH or long-range PCR over the recombination sites. Nanopore sequencing provides a cost convenient method to detect such underrated off-target effects, suggesting its use for additional quality assessment of gene editing in mice and also other model organisms.
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Registered trials
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 Socratic graph.