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Updated: Feb 14, 2026

A Mouse Model of Lumbar Spine Instability
Published on: April 23, 2021
Calcineurin knockout mice show a selective loss of small spines
Hitoshi Okazaki1, Akiko Hayashi-Takagi2, Akira Nagaoka3
1Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Abstract:
Calcineurin is required for long-term depression and activity-dependent spine shrinkage, and calcineurin mutations have been identified in patients with schizophrenia. Moreover, mice with conditional knockout of calcineurin B (CNB-KO) exhibit behavioral abnormalities suggestive of schizophrenia. Changes in the dendritic spines of these mice, however, have not been investigated. We therefore examined the dendritic spines of CNB-KO mice, and observed a significant reduction in small spines and an increase in large spines in the prefrontal and visual cortices. The effect of CNB-KO on the spine sizes was relatively moderate, possibly due to the presence of spontaneous fluctuations (dynamics) in the dendritic spines themselves. Thus, CNB-KO mice showed a spine phenotype similar to those recently reported in patients with schizophrenia.
Insights
Calcineurin B knockout mice show altered dendritic spine size, mirroring changes seen in schizophrenia patients. This suggests a potential role for calcineurin in the neurobiology of schizophrenia.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Calcineurin is crucial for synaptic plasticity, including long-term depression and spine shrinkage.
- Calcineurin mutations are linked to schizophrenia, and related mouse models display behavioral deficits.
- The impact of calcineurin deficiency on dendritic spine morphology in these models remains unexamined.
Purpose of the Study:
- To investigate the dendritic spine phenotype in mice with conditional knockout of calcineurin B (CNB-KO).
- To determine if CNB-KO mice exhibit spine alterations relevant to schizophrenia.
Main Methods:
- Examined dendritic spines in the prefrontal and visual cortices of CNB-KO mice.
- Quantified spine size distribution and compared it to wild-type controls.
Main Results:
- CNB-KO mice displayed a significant reduction in small dendritic spines.
- An increase in large dendritic spines was observed in the prefrontal and visual cortices of CNB-KO mice.
- The observed spine phenotype was moderate, potentially influenced by spine dynamics.
Conclusions:
- CNB-KO mice exhibit a dendritic spine phenotype resembling that reported in schizophrenia patients.
- These findings support a role for calcineurin in the structural changes of dendritic spines associated with schizophrenia.
- CNB-KO mice serve as a valuable model for studying the neurobiological underpinnings of schizophrenia.
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