Related Experiment Video
Updated: Jun 7, 2026
Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors
Published on: May 10, 2015
The deletion of the microtubule-associated STOP protein affects the serotonergic mouse brain network
Vincent Fournet1, Marion Jany, Véronique Fabre
1INSERM UMRS 952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris, France.
Abstract:
The deletion of microtubule-associated protein stable tubule only polypeptide (STOP) leads to neuroanatomical, biochemical and severe behavioral alterations in mice, partly alleviated by antipsychotics. Therefore, STOP knockout (KO) mice have been proposed as a model of some schizophrenia-like symptoms. Preliminary data showed decreased brain serotonin (5-HT) tissue levels in STOP KO mice. As literature data demonstrate various interactions between microtubule-associated proteins and 5-HT, we characterized some features of the serotonergic neurotransmission in STOP KO mice. In the brainstem, mutant mice displayed higher tissue 5-HT levels and in vivo synthesis rate, together with marked increases in 5-HT transporter densities and 5-HT1A autoreceptor levels and electrophysiological sensitivity, without modification of the serotonergic soma number. Conversely, in projection areas, STOP KO mice exhibited lower 5-HT levels and in vivo synthesis rate, associated with severe decreases in 5-HT transporter densities, possibly related to reduced serotonergic terminals. Mutant mice also displayed a deficit of adult hippocampal neurogenesis, probably related to both STOP deletion and 5-HT depletion. Finally, STOP KO mice exhibited a reduced anxiety- and, probably, an increased helpness-status, that could be because of the strong imbalance of the serotonin neurotransmission between somas and terminals. Altogether, these data suggested that STOP deletion elicited peculiar 5-HT disconnectivity.
Insights
Mice lacking the stable tubule only polypeptide (STOP) protein show altered serotonin neurotransmission, impacting brain regions and potentially modeling schizophrenia-like symptoms. This suggests STOP deletion causes significant serotonin pathway disconnectivity.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Stable tubule only polypeptide (STOP) protein is crucial for microtubule stability.
- STOP knockout (KO) mice exhibit behavioral and neuroanatomical changes, suggesting a model for schizophrenia-like symptoms.
- Preliminary studies indicate altered serotonin (5-HT) levels in STOP KO mice.
Purpose of the Study:
- To investigate the impact of STOP deletion on serotonergic neurotransmission in STOP KO mice.
- To characterize alterations in serotonin synthesis, transporter, and receptor function.
- To explore the relationship between STOP deletion, serotonin imbalance, and behavioral phenotypes.
Main Methods:
- Comparative analysis of brainstem and projection area tissue.
- In vivo measurements of serotonin synthesis rates.
- Assessment of 5-HT transporter and 5-HT1A autoreceptor densities and function.
- Evaluation of adult hippocampal neurogenesis.
- Behavioral testing for anxiety and helplessness.
Main Results:
- STOP KO mice showed increased brainstem 5-HT levels, synthesis, 5-HT transporter, and 5-HT1A autoreceptor function.
- Conversely, projection areas exhibited decreased 5-HT levels, synthesis, and 5-HT transporter densities.
- A deficit in adult hippocampal neurogenesis was observed in STOP KO mice.
- STOP KO mice displayed reduced anxiety and increased helplessness.
Conclusions:
- STOP deletion induces a significant imbalance in central serotonin neurotransmission, characterized by regional disconnectivity.
- Altered serotonergic pathways in STOP KO mice may underlie observed behavioral deficits and neurogenesis impairment.
- These findings highlight the critical role of STOP protein in regulating brain serotonin system homeostasis.
