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

UNLABELLED

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 knockout () 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 mice using a standardized test battery. In the social interaction test in a novel environment, 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, 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 mice exhibit selective behavioral impairments depending on task demands and environmental context. Our findings provide the first behavioral characterization of mice and offer new insights into the functional role of SEPT3, laying a foundation for future investigation into its molecular and circuit-level mechanisms.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s13041-025-01243-5.