ArticleProceedings of the National Academy of Sciences of the United States of America2011
Second-generation high-throughput forward genetic screen in mice to isolate subtle behavioral mutants.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
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- Forward genetic approach for behavioral neuroscience using animal models.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2020Article
- A novel mutation in Slc2a4 as a mouse model of fatigue.Genes, brain, and behavior · 2019Article
- Robust mouse tracking in complex environments using neural networks.Communications biology · 2019Article
- Whole exome sequencing reveals a functional mutation in the GAIN domain of the Bai2 receptor underlying a forward mutagenesis hyperactivity QTL.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Article
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- A strategy to identify dominant point mutant modifiers of a quantitative trait.G3 (Bethesda, Md.) · 2014Article
- Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen.Nature communications · 2014Article
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Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Forward genetic screens have been highly successful in revealing roles of genes and pathways in complex biological events. Traditionally these screens have focused on isolating mutants with the greatest phenotypic deviance, with the hopes of discovering genes that are central to the biological event being investigated. Behavioral screens in mice typically use simple activity-based assays as endophenotypes for more complex emotional states of the animal. They generally set the selection threshold for a putative mutant at 3 SDs (z score of 3) from the average behavior of normal animals to minimize false-positive results. Behavioral screens using a high threshold for detection have generally had limited success, with high false-positive rates and subtle phenotypic differences that have made mapping and cloning difficult. In addition, targeted reverse genetic approaches have shown that when genes central to behaviors such as open field behavior, psychostimulant response, and learning and memory tasks are mutated, they produce subtle phenotypes that differ from wild-type animals by 1 to 2 SDs (z scores of 1 to 2). We have conducted a second-generation (G2) dominant N-ethyl-N-nitrosourea (ENU) screen especially designed to detect subtle behavioral mutants for open field activity and psychostimulant response behaviors. We successfully detect mutant lines with only 1 to 2 SD shifts in mean response compared with wild-type control animals and present a robust statistical and methodological framework for conducting such forward genetic screens. Using this methodology we have screened 229 ENU mutant lines and have identified 15 heritable mutant lines. We conclude that for screens in mice that use activity-based endophenotypic measurements for complex behavioral states, this G2 screening approach yields better results.
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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.