title: Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice.
abstract: Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait "anxiety". We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior. We identified and confirmed sex-independent differences in the basal expression of 13 candidate genes, using tissue from the entire brain, including coronin 7 (Coro7), cathepsin B (Ctsb), muscleblind-like 1 (Mbnl1), metallothionein 1 (Mt1), solute carrier family 25 member 17 (Slc25a17), tribbles homolog 2 (Trib2), zinc finger protein 672 (Zfp672), syntaxin 3 (Stx3), ATP-binding cassette, sub-family A member 2 (Abca2), ectonucleotide pyrophosphatase/phosphodiesterase 5 (Enpp5), high mobility group nucleosomal binding domain 3 (Hmgn3) and pyruvate dehydrogenase beta (Pdhb). Additionally, we confirmed brain region-specific differences in the expression of synaptotagmin 4 (Syt4).Our identification of about 90 polymorphisms in Ctsb suggested that this gene might play a critical role in shaping our mouse model's behavioral endophenotypes. Indeed, the assessment of anxiety-related and depression-like behaviors of Ctsb knock-out mice revealed an increase in depression-like behavior in females. Altogether, our results suggest that Ctsb has significant effects on emotionality, irrespective of the tested mouse strain, making it a promising target for future pharmacotherapy.
authors: Max Planck Institute of Psychiatry, Munich, Germany. czibere@mpipsykl.mpg.de
authors: Ludwig
authors: L
authors: Czibere
authors: Laura A
authors: LA
authors: Baur
authors: Anke
authors: A
authors: Wittmann
authors: Katja
authors: K
authors: Gemmeke
authors: Andrea
authors: A
authors: Steiner
authors: Peter
authors: P
authors: Weber
authors: Benno
authors: B
authors: Pütz
authors: Nafees
authors: N
authors: Ahmad
authors: Mirjam
authors: M
authors: Bunck
authors: Cornelia
authors: C
authors: Graf
authors: Regina
authors: R
authors: Widner
authors: Claudia
authors: C
authors: Kühne
authors: Markus
authors: M
authors: Panhuysen
authors: Boris
authors: B
authors: Hambsch
authors: Gabriele
authors: G
authors: Rieder
authors: Thomas
authors: T
authors: Reinheckel
authors: Christoph
authors: C
authors: Peters
authors: Florian
authors: F
authors: Holsboer
authors: Rainer
authors: R
authors: Landgraf
authors: Jan M
authors: JM
authors: Deussing
mesh_terms: D000818:Animals; D001007:Anxiety / Q000201:enzymology* / Q000235:genetics*; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D002401:Cathepsin B / Q000172:deficiency / Q000235:genetics*; D058068:Endophenotypes; D005260:Female; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D002401:Cathepsin B