Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice.
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...
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2011
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oai:doaj.org-article:5a2ad2e33cd54f34a13d737be0d182ea2021-11-18T06:47:08ZProfiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice.1932-620310.1371/journal.pone.0023604https://doaj.org/article/5a2ad2e33cd54f34a13d737be0d182ea2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21897848/?tool=EBIhttps://doaj.org/toc/1932-6203Behavioral 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.Ludwig CzibereLaura A BaurAnke WittmannKatja GemmekeAndrea SteinerPeter WeberBenno PützNafees AhmadMirjam BunckCornelia GrafRegina WidnerClaudia KühneMarkus PanhuysenBoris HambschGabriele RiederThomas ReinheckelChristoph PetersFlorian HolsboerRainer LandgrafJan M DeussingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23604 (2011) |
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Medicine R Science Q Ludwig Czibere Laura A Baur Anke Wittmann Katja Gemmeke Andrea Steiner Peter Weber Benno Pütz Nafees Ahmad Mirjam Bunck Cornelia Graf Regina Widner Claudia Kühne Markus Panhuysen Boris Hambsch Gabriele Rieder Thomas Reinheckel Christoph Peters Florian Holsboer Rainer Landgraf Jan M Deussing Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice. |
| description |
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. |
| format |
article |
| author |
Ludwig Czibere Laura A Baur Anke Wittmann Katja Gemmeke Andrea Steiner Peter Weber Benno Pütz Nafees Ahmad Mirjam Bunck Cornelia Graf Regina Widner Claudia Kühne Markus Panhuysen Boris Hambsch Gabriele Rieder Thomas Reinheckel Christoph Peters Florian Holsboer Rainer Landgraf Jan M Deussing |
| author_facet |
Ludwig Czibere Laura A Baur Anke Wittmann Katja Gemmeke Andrea Steiner Peter Weber Benno Pütz Nafees Ahmad Mirjam Bunck Cornelia Graf Regina Widner Claudia Kühne Markus Panhuysen Boris Hambsch Gabriele Rieder Thomas Reinheckel Christoph Peters Florian Holsboer Rainer Landgraf Jan M Deussing |
| author_sort |
Ludwig Czibere |
| title |
Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice. |
| title_short |
Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice. |
| title_full |
Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice. |
| title_fullStr |
Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice. |
| title_full_unstemmed |
Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a novel candidate gene for emotionality in mice. |
| title_sort |
profiling trait anxiety: transcriptome analysis reveals cathepsin b (ctsb) as a novel candidate gene for emotionality in mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/5a2ad2e33cd54f34a13d737be0d182ea |
| work_keys_str_mv |
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