Profiling Trait Anxiety: Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice

被引：46

作者：

Czibere, Ludwig ^{[1
]}

Baur, Laura A. ^{[1
]}

Wittmann, Anke ^{[1
]}

Gemmeke, Katja ^{[1
]}

Steiner, Andrea ^{[1
]}

Weber, Peter ^{[1
]}

Puetz, Benno ^{[1
]}

Ahmad, Nafees ^{[1
,2
]}

Bunck, Mirjam ^{[1
]}

Graf, Cornelia ^{[1
,2
]}

Widner, Regina ^{[1
]}

Kuehne, Claudia ^{[1
]}

Panhuysen, Markus ^{[3
]}

Hambsch, Boris ^{[1
]}

Rieder, Gabriele ^{[4
]}

Reinheckel, Thomas ^{[5
]}

Peters, Christoph ^{[5
]}

Holsboer, Florian ^{[1
]}

Landgraf, Rainer ^{[1
]}

Deussing, Jan M. ^{[1
,2
]}

机构：

[1] Max Planck Inst Psychiat, Munich, Germany

[2] Helmholtz Zentrum Munchen, Inst Dev Genet, Neuherberg, Germany

[3] Affectis Pharmaceut, Martinsried, Germany

[4] Univ Munich, Max Von Pettenkofer Inst, Munich, Germany

[5] Univ Freiburg, Fac Biol, Inst Mol Med & Cell Res, Freiburg, Germany

来源：

PLOS ONE | 2011年 / 6卷 / 08期

关键词：

SYNAPTOTAGMIN-IV; METALLOTHIONEIN-I/II; MOUSE-BRAIN; WILD-TYPE; DEPRESSION; EXPRESSION; VASOPRESSIN; SYSTEM; MODEL; P2RX7;

D O I：

10.1371/journal.pone.0023604

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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