ArticlePloS one2010
A transposon in Comt generates mRNA variants and causes widespread expression and behavioral differences among mice.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 49 citations in OpenAlex.
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- Detection of Differentially Expressed Cleavage Site Intervals Within 3' Untranslated Regions Using CSI-UTR Reveals Regulated Interaction Motifs.Frontiers in genetics · 2019Article
- Comparison and Functional Genetic Analysis of Striatal Protein Expression Among Diverse Inbred Mouse Strains.Frontiers in molecular neuroscience · 2019Article
- Mouse germ line mutations due to retrotransposon insertions.Mobile DNA · 2019Review
- Post-genomic behavioral genetics: From revolution to routine.Genes, brain, and behavior · 2018Review
- Systems Genetic Analysis in GeneNetwork.org.Current protocols in neuroscience · 2017Article
- GeneNetwork: A Toolbox for Systems Genetics.Methods in molecular biology (Clifton, N.J.) · 2017Article
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- Out of the bottleneck: the Diversity Outcross and Collaborative Cross mouse populations in behavioral genetics research.Mammalian genome : official journal of the International Mammalian Genome Society · 2014Review
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- Genetics of gene expression in CNS.International review of neurobiology · 2014Review
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- How do mammalian transposons induce genetic variation? A conceptual framework: the age, structure, allele frequency, and genome context of transposable elements may define their wide-ranging biological impacts.BioEssays : news and reviews in molecular, cellular and developmental biology · 2013Article
- Fronto-temporal-mesolimbic gene expression and heritable differences in amphetamine-disrupted sensorimotor gating in rats.Psychopharmacology · 2012Article
- Transposable elements and viruses as factors in adaptation and evolution: an expansion and strengthening of the TE-Thrust hypothesis.Ecology and evolution · 2012Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCatechol-O-methyltransferase (COMT) is a key enzyme responsible for the degradation of dopamine and norepinephrine. COMT activity influences cognitive and emotional states in humans and aggression and drug responses in mice. This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits. METHODOLOGY/PRINCIPAL
findingsWe examined Comt expression in multiple tissues in over 100 diverse strains and several genetic crosses. Differences in expression map back to Comt and are generated by a 230 nt insertion of a B2 short interspersed element (B2 SINE) in the proximal 3' UTR of Comt in C57BL/6J. This transposon introduces a premature polyadenylation signal and creates a short 3' UTR isoform. The B2 SINE is shared by a subset of strains, including C57BL/6J, A/J, BALB/cByJ, and AKR/J, but is absent in others, including DBA/2J, FVB/NJ, SJL/J, and wild subspecies. The short isoform is associated with increased protein expression in prefrontal cortex and hippocampus relative to the longer ancestral isoform. The Comt variant causes downstream differences in the expression of genes involved in synaptic function, and also modulates phenotypes such as dopamine D1 and D2 receptor binding and pharmacological responses to haloperidol. CONCLUSIONS/SIGNIFICANCE: We have precisely defined the B2 SINE as the source of variation in Comt and demonstrated that a transposon in a 3' UTR can alter mRNA isoform use and modulate behavior. The recent fixation of the variant in a subset of strains may have contributed to the rapid divergence of inbred strains.
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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.