简介：AbstractObjective:The asparagine-linked glycosylation 13 homolog (Alg13) has been identified as causative for congenital disorders of glycosylation type I with epilepsy. The aim of this study was to determine whether mice carrying a mutated version of Alg13 could be used as a model for epileptic encephalopathies or congenital disorders of glycosylation type I.Methods:A model of epileptic encephalopathy was established in C57BL/6 mice by introducing mutations in Alg13 via the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system. All surgical procedures were approved by the Institutional Animal Care and Use Committee of Shanghai Jiao Tong University (A2016084) on October 8, 2016.Results:Mice with 3 different mutations, Alg13-54nt, Alg13-5nt and Alg13-4nt, all of which are located in Alg13 transcript variant 1, were created. The Alg13-5nt mice exhibited spontaneous seizures similar to patients with Alg13 mutations, suggesting that they could be used as a model for epilepsy. Western blot analysis demonstrated that Alg13-5nt mice had lower levels of Alg13 expression than wild-type mice. Video observations showed that two of the 17 Alg13-5nt mice had stage 5 seizures involving jumping and falling, while 12 had stage 3 seizures with head nodding.Conclusion:The Alg13 mouse model provides an outstanding tool for studying epileptic encephalopathies and investigating different aspects of defects in glycosylation or other post-translational modification that cannot be assessed in patients or cell culture systems.