Cofilin-1: a modulator of anxiety in mice.
The genes involved in conferring susceptibility to anxiety remain obscure. We developed a new method to identify genes at quantitative trait loci (QTLs) in a population of heterogeneous stock mice descended from known progenitor strains. QTLs were partitioned into intervals that can be summarized by a single phylogenetic tree among progenitors and intervals tested for consistency with alleles influencing anxiety at each QTL. By searching for common Gene Ontology functions in candidate genes positioned within those intervals, we identified actin depolymerizing factors (ADFs), including cofilin-1 (Cfl1), as genes involved in regulating anxiety in mice. There was no enrichment for function in the totality of genes under each QTL, indicating the importance of phylogenetic filtering. We confirmed experimentally that forebrain-specific inactivation of Cfl1 decreased anxiety in knockout mice. Our results indicate that similarity of function of mammalian genes can be used to recognize key genetic regulators of anxiety and potentially of other emotional behaviours.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Martin
M
Goodson
Marco B
MB
Rust
Walter
W
Witke
David
D
Bannerman
Richard
R
Mott
Chris P
CP
Ponting
Jonathan
J
Flint
D000818:Animals; D001007:Anxiety / Q000235:genetics*; D051338:Cofilin 1 / Q000235:genetics*; D008297:Male; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D058977:Molecular Sequence Annotation; D009154:Mutation; D010802:Phylogeny; D016548:Prosencephalon / Q000378:metabolism; D040641:Quantitative Trait Loci
D051338:Cofilin 1