Evidence map›Paper›PMID 41838061›Full record

ArticleArchives of toxicology2026

Integrated transcriptomic and variant analysis reveals molecular mechanisms of pyrethroid resistance in a genetically homogenized Cas9 strain of Aedes aegypti.

Dylan Brown, Reese Houck, Nannan Liu

Abstract read
In one paragraph

Article in Archives of toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Dylan BrownDepartment of Entomology and Plant Pathology, School of Agriculture, Auburn University, Auburn, AL, 36849, USA.
Reese HouckDepartment of Entomology and Plant Pathology, School of Agriculture, Auburn University, Auburn, AL, 36849, USA.
Nannan LiuDepartment of Entomology and Plant Pathology, School of Agriculture, Auburn University, Auburn, AL, 36849, USA. liunann@auburn.edu.ORCID 0000-0002-3088-9387

Funding

AAES Hatch/Multistate Grants ALA015-1-16009AAES Hatch/Multistate Grants ALA015-1-19148
6 · The paper itself

Abstract

Insecticide resistance, a central problem in insecticide toxicology, in Aedes aegypti continues to undermine vector control efforts worldwide. Although transcriptomic studies have identified numerous resistance-associated genes, differences in genetic background between resistant and susceptible strains often obscure which changes are directly linked to resistance. To reduce background variability, we generated a genetically homogenized pyrethroid-resistant Cas9 strain (PRCas9) by repeatedly backcrossing a susceptible Cas9 strain (exu-Cas9 line) with a highly permethrin-resistant Puerto Rico (PR) strain. PRCas9 retained extreme resistance comparable to the parental PR strain (> 18,000-fold resistance ratio) and was further analyzed alongside the PR and Cas9 strains using RNA-seq. Using this controlled genetic background, transcriptomic profiling identified > 70 differentially expressed genes between resistant and susceptible mosquitoes, revealing reproducible resistance-associated detoxification in insecticide toxicology signatures dominated by cytochrome P450s and carboxylesterases. qRT-PCR validated elevated expression of key detoxification candidates. Variant and promoter sequencing further revealed unique SNPs in detoxification genes, including CYP9J23, CYP9J28, and venom carboxylesterase-6, as well as distinct variants in NOX4-art, a NADPH oxidase involved in reactive oxygen species (ROS) production. Gene ontology analysis supported enrichment of detoxification-related molecular functions. Increased NOX4-art expression, together with these regulatory variants, suggests a potential role for ROS-linked regulatory pathways in coordinating detoxification gene activation. This study demonstrates the value of a genetically homogenized resistant Cas9 background for dissecting resistance mechanisms while identifying candidate genes and regulatory elements contributing to pyrethroid resistance. PRCas9 provides a powerful platform for future CRISPR-based functional analyses in insect toxicology aimed at improving vector control strategies.

Indexed as

AedesInsecticide ResistanceInsecticidesPyrethrinsTranscriptomeAnimalsGene Expression ProfilingPolymorphism, Single NucleotideInsecticidesPyrethrinsAedes aegyptiGenetically homogenized Cas9 strainPyrethroid resistanceResistance mechanismsSNP analysisTranscriptomics

Identifiers

PMID41838061
PMCPMC13221410

What Socratic holds

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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 Socratic graph.