Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities

Abstract The septin cytoskeleton is recognized as the fourth component of the cytoskeleton. Septin 3 (SEPT3)/G-septin is a neuron-selective subunit of the septin family and is widely expressed in mature neurons. We previously demonstrated that SEPT3 regulates long-term potentiation (L-LTP)-dependent...

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Main Authors: Natsumi Ageta-Ishihara, Keizo Takao, Tsuyoshi Miyakawa, Makoto Kinoshita
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Molecular Brain
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Online Access:https://doi.org/10.1186/s13041-025-01243-5
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author Natsumi Ageta-Ishihara
Keizo Takao
Tsuyoshi Miyakawa
Makoto Kinoshita
author_facet Natsumi Ageta-Ishihara
Keizo Takao
Tsuyoshi Miyakawa
Makoto Kinoshita
author_sort Natsumi Ageta-Ishihara
collection DOAJ
description Abstract The septin cytoskeleton is recognized as the fourth component of the cytoskeleton. Septin 3 (SEPT3)/G-septin is a neuron-selective subunit of the septin family and is widely expressed in mature neurons. We previously demonstrated that SEPT3 regulates long-term potentiation (L-LTP)-dependent extension of smooth endoplasmic reticulum (sER) into dendritic spines of granule cells in the hippocampal dentate gyrus (DG), and that Sept3 knockout (Sept3 −/−) mice exhibited impairments in DG-dependent spatial long-term memory. However, the broader behavioral consequences of SEPT3 deficiency remain largely unexplored. To address this, we conducted comprehensive behavioral phenotyping of male Sept3 −/− mice using a standardized test battery. In the social interaction test in a novel environment, Sept3 −/− mice showed increased contact frequency and interaction time. In contrast, performance in the three-chamber social interaction test was comparable to wild-type mice, indicating context-dependent deficits. In contextual fear conditioning, Sept3 −/− mice displayed reduced freezing 24 h after training, but not 35 days later. In the T-maze forced alternation task, deficits were observed in choice accuracy and latency. These results demonstrate that Sept3 −/− mice exhibit selective behavioral impairments depending on task demands and environmental context. Our findings provide the first behavioral characterization of Sept3 −/− mice and offer new insights into the functional role of SEPT3, laying a foundation for future investigation into its molecular and circuit-level mechanisms.
format Article
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issn 1756-6606
language English
publishDate 2025-08-01
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spelling doaj-art-20fc3de4fa35471da3790c9dd31748d62025-08-24T11:57:52ZengBMCMolecular Brain1756-66062025-08-011811610.1186/s13041-025-01243-5Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalitiesNatsumi Ageta-Ishihara0Keizo Takao1Tsuyoshi Miyakawa2Makoto Kinoshita3Department of Biomolecular Science, Faculty of Science, Toho UniversityDepartment of Behavioral Physiology, Faculty of Medicine, University of ToyamaDivision of Systems Medical Science, Center for Medical Science, Fujita Health UniversityDepartment of Molecular Biology, Division of Biological Sciences, Nagoya University Graduate School of ScienceAbstract The septin cytoskeleton is recognized as the fourth component of the cytoskeleton. Septin 3 (SEPT3)/G-septin is a neuron-selective subunit of the septin family and is widely expressed in mature neurons. We previously demonstrated that SEPT3 regulates long-term potentiation (L-LTP)-dependent extension of smooth endoplasmic reticulum (sER) into dendritic spines of granule cells in the hippocampal dentate gyrus (DG), and that Sept3 knockout (Sept3 −/−) mice exhibited impairments in DG-dependent spatial long-term memory. However, the broader behavioral consequences of SEPT3 deficiency remain largely unexplored. To address this, we conducted comprehensive behavioral phenotyping of male Sept3 −/− mice using a standardized test battery. In the social interaction test in a novel environment, Sept3 −/− mice showed increased contact frequency and interaction time. In contrast, performance in the three-chamber social interaction test was comparable to wild-type mice, indicating context-dependent deficits. In contextual fear conditioning, Sept3 −/− mice displayed reduced freezing 24 h after training, but not 35 days later. In the T-maze forced alternation task, deficits were observed in choice accuracy and latency. These results demonstrate that Sept3 −/− mice exhibit selective behavioral impairments depending on task demands and environmental context. Our findings provide the first behavioral characterization of Sept3 −/− mice and offer new insights into the functional role of SEPT3, laying a foundation for future investigation into its molecular and circuit-level mechanisms.https://doi.org/10.1186/s13041-025-01243-5SeptinKnockout miceBehavioral phenotypingSocial interactionContextual fear conditioningSpatial working memory
spellingShingle Natsumi Ageta-Ishihara
Keizo Takao
Tsuyoshi Miyakawa
Makoto Kinoshita
Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities
Molecular Brain
Septin
Knockout mice
Behavioral phenotyping
Social interaction
Contextual fear conditioning
Spatial working memory
title Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities
title_full Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities
title_fullStr Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities
title_full_unstemmed Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities
title_short Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities
title_sort comprehensive behavioral phenotyping of male septin 3 deficient mice reveals task specific abnormalities
topic Septin
Knockout mice
Behavioral phenotyping
Social interaction
Contextual fear conditioning
Spatial working memory
url https://doi.org/10.1186/s13041-025-01243-5
work_keys_str_mv AT natsumiagetaishihara comprehensivebehavioralphenotypingofmaleseptin3deficientmicerevealstaskspecificabnormalities
AT keizotakao comprehensivebehavioralphenotypingofmaleseptin3deficientmicerevealstaskspecificabnormalities
AT tsuyoshimiyakawa comprehensivebehavioralphenotypingofmaleseptin3deficientmicerevealstaskspecificabnormalities
AT makotokinoshita comprehensivebehavioralphenotypingofmaleseptin3deficientmicerevealstaskspecificabnormalities