ArticleEpilepsia2020
Collaborative Cross mice reveal extreme epilepsy phenotypes and genetic loci for seizure susceptibility.
Article in Epilepsia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Hippocampal snRNA-seq in Collaborative Cross reveals molecular signatures of cognitive resilience independent of chronological aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Integrative Principal Component-QTL Mapping Identifies Genetic Modifiers of Tumor and Metabolic Traits inInternational journal of molecular sciences · 2026Article
- Mapping Genetic Modifiers of Polyp Formation inCells · 2026Article
- Systematic cell-type resolved transcriptomes of 8 tissues in 8 lab and wild-derived mouse strains capture global and local expression variation.Cell genomics · 2026Article
- Behavior Decoding Delineates Seizure Microfeatures and Associated Sudden Death Risks in Mouse Models of Epilepsy.Annals of neurology · 2026Article
- Article
- Challenges and future directions of SUDEP models.Lab animal · 2024Review
- Identification of a genetic region linked to tolerance to MRSA infection using Collaborative Cross mice.PLoS genetics · 2024Article
- Psychiatric risk gene Transcription Factor 4 (TCF4) regulates the density and connectivity of distinct inhibitory interneuron subtypes.Molecular psychiatry · 2023Article
- Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome.Microbiome · 2023Article
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- Article
- Forward genetic screen of homeostatic antibody levels in the Collaborative Cross identifies MBD1 as a novel regulator of B cell homeostasis.PLoS genetics · 2022Article
- Fine mapping and candidate gene analysis of a dravet syndrome modifier locus on mouse chromosome 11.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Article
- Morphine analgesia in male inbred genetic diversity mice recapitulates the among-individual variance in response to morphine in humans.Animal models and experimental medicine · 2022Article
- Powerful, efficient QTL mapping in Drosophila melanogaster using bulked phenotyping and pooled sequencing.Genetics · 2022Article
- Ictal neural oscillatory alterations precede sudden unexpected death in epilepsy.Brain communications · 2022Article
- New inroads into the brain circuits and network dynamics behind sudden unexpected death in epilepsy.Brain communications · 2022Article
- Paradoxical hyperexcitability from NaCell reports · 2021Article
- Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research.Genetics · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveAnimal studies remain essential for understanding mechanisms of epilepsy and identifying new therapeutic targets. However, existing animal models of epilepsy do not reflect the high level of genetic diversity found in the human population. The Collaborative Cross (CC) population is a genetically diverse recombinant inbred panel of mice. The CC offers large genotypic and phenotypic diversity, inbred strains with stable genomes that allow for repeated phenotypic measurements, and genomic tools including whole genome sequence to identify candidate genes and candidate variants.
methodsWe evaluated multiple complex epileptic traits in a sampling of 35 CC inbred strains using the flurothyl-induced seizure and kindling paradigm. We created an F2 population of 297 mice with extreme seizure susceptibility and performed quantitative trait loci (QTL) mapping to identify genomic regions associated with seizure sensitivity. We used quantitative RNA sequencing from CC hippocampal tissue to identify candidate genes and whole genome sequence to identify genetic variants likely affecting gene expression.
resultsWe identified new mouse models with extreme seizure susceptibility, seizure propagation, epileptogenesis, and SUDEP (sudden unexpected death in epilepsy). We performed QTL mapping and identified one known and seven novel loci associated with seizure sensitivity. We combined whole genome sequencing and hippocampal gene expression to pinpoint biologically plausible candidate genes (eg, Gabra2) and variants associated with seizure sensitivity. SIGNIFICANCE: New mouse models of epilepsy are needed to better understand the complex genetic architecture of seizures and to identify therapeutics. We performed a phenotypic screen utilizing a novel genetic reference population of CC mice. The data we provide enable the identification of protective/risk genes and novel molecular mechanisms linked to complex seizure traits that are currently challenging to study and treat.
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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 OpenQuestion graph.