Journal
SCIENCE
Volume 327, Issue 5967, Pages 863-866Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1181886
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Funding
- NIH [MH079513, MH060478, NS052819, HD055177, GM07739]
- United Negro College
- Burroughs Wellcome Foundation
- International Mental Health Research Organization
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Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.
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