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Updated: Jan 14, 2026
Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein
Published on: March 16, 2022
Construction of pathogenic Sec16a mutation mouse model using CRISPR/Cas9
Yaqiang Hu1, Zhiyang Zeng2, Xinyu Ming1
1Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Background:
SEC16A is a pivotal protein that facilitates the transport of proteins from the endoplasmic reticulum to the Golgi apparatus. Utilizing the protein structure function database, a potentially pathogenic mutation site (NM_014866.1: c.4606C>G(p.L1536V)) was pinpointed within the conserved central core region of the human SEC16A protein, a component integral to the COPII complex assembly.
Methods:
Leveraging information on human gene mutations and aligning human and mouse protein amino acid sequences, the Sec16aL1551V/L1551V mouse model was successfully developed using CRISPR/Cas9 technology.
Results:
Two behavioral experiments, namely novel object recognition and cued fear conditioning, revealed that Sec16aL1551V/L1551V mice demonstrated a phenotype of neurological impairment, evidenced by diminished abilities in learning and memory. Furthermore, while undergoing tail suspension, the Sec16aL1551V/L1551V mice displayed a distinctive limb clasping behavior, a characteristic typically associated with mouse models of chronic neurodegenerative diseases.
Conclusion:
The Sec16aL1551V/L1551V mouse model developed in this study providing a powerful tool for better understanding of the pathogenic mechanisms of Sec16a gene mutations in brain dysfunction diseases.
