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CD146 deletion in the nervous system impairs appetite, locomotor activity and spatial learning in mice
Tao Tu1, Qian Gao, Yongting Luo
1Key Laboratory of Protein and Peptide Pharmaceuticals, CAS-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China ; University of Chinese Academy of Sciences, Beijing, China.
Abstract:
Cell adhesion molecules (CAMs) are crucial effectors for the development and maintenance of the nervous system. Mutations in human CAM genes are linked to brain disorders and psychological diseases, and CAM knockout mice always exhibit similar behavioral abnormalities. CD146 is a CAM of the immunoglobulin superfamily that interacts with Neurite Outgrowth Factor and involved in neurite extension in vitro. However, little is known about its in vivo function in the nervous system. In this study, we used a murine CD146 nervous system knockout (CD146(ns-ko)) model. We found that the brains of some CD146(ns-ko) mice were malformed with small olfactory bulbs. CD146(ns-ko) mice exhibited lower body weights and smaller food intake when compared with wild type littermates. Importantly, behavior tests revealed that CD146(ns-ko) mice exhibited significant decreased locomotor activity and impaired capacity for spatial learning and memory. Our results demonstrate that CD146 is important for mammalian nervous system development and proper behavior patterns.
Insights
Cell adhesion molecule CD146 is vital for nervous system development. Its absence in mice caused brain malformations, reduced growth, and impaired learning and memory, highlighting CD146
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Cell adhesion molecules (CAMs) are essential for nervous system development and maintenance.
- Mutations in human CAM genes are associated with neurological and psychological disorders.
- CD146, an immunoglobulin superfamily CAM, promotes neurite extension in vitro, but its in vivo nervous system function is largely unknown.
Purpose of the Study:
- To investigate the in vivo function of CD146 in the mammalian nervous system using a knockout mouse model.
Main Methods:
- Generation of a murine CD146 nervous system-specific knockout (CD146(ns-ko)) model.
- Comparative analysis of brain morphology, body weight, food intake, and behavioral tests between CD146(ns-ko) mice and wild-type littermates.
Main Results:
- CD146(ns-ko) mice displayed brain malformations, including smaller olfactory bulbs in some individuals.
- These mice exhibited reduced body weight and food intake compared to controls.
- Behavioral assessments revealed significantly decreased locomotor activity and impaired spatial learning and memory in CD146(ns-ko) mice.
Conclusions:
- CD146 plays a critical role in mammalian nervous system development.
- CD146 is essential for establishing normal behavior patterns, including motor activity and cognitive functions like spatial learning and memory.
