A genetic variant BDNF polymorphism alters extinction learning in both mouse and human.
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ABSTRACT:
SUBMITTER: Soliman F
PROVIDER: S-EPMC2829261 | biostudies-literature | 2010 Feb
REPOSITORIES: biostudies-literature
Publications
A genetic variant BDNF polymorphism alters extinction learning in both mouse and human.
Soliman Fatima F Glatt Charles E CE Bath Kevin G KG Levita Liat L Jones Rebecca M RM Pattwell Siobhan S SS Jing Deqiang D Tottenham Nim N Amso Dima D Somerville Leah H LH Voss Henning U HU Glover Gary G Ballon Douglas J DJ Liston Conor C Teslovich Theresa T Van Kempen Tracey T Lee Francis S FS Casey B J BJ
Science (New York, N.Y.) 20100114 5967
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 exting ...[more]
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Project description:A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.
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2011-08-07 | E-GEOD-31063 | biostudies-arrayexpress
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2011-08-08 | GSE31063 | GEO
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