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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BMC
2025-08-01
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| 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 |
| id | doaj-art-20fc3de4fa35471da3790c9dd31748d6 |
| institution | Kabale University |
| issn | 1756-6606 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Molecular Brain |
| 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 |