The Sez6 gene primarily encodes a Seizure-related homolog protein 6 (SEZ6), a cell-surface type I transmembrane glycoprotein that is an N-glycosylated protein containing five short consensus repeat (SCR)/sushi domains and two or three CUB domains in its extracellular domain ^[1]. Gene expression is highly restricted in normal adult tissues, found almost exclusively in the central nervous system (CNS), particularly in neurons (e.g., in the cerebral cortex, hippocampus), with low expression in the testis and some gastrointestinal tissues. SEZ6 is involved in neuronal development and function, notably in regulating dendrite elongation and branching, synaptic plasticity, and may also function as a complement regulator by inhibiting C3 convertases, in addition to being a novel trafficking protein of the kainate receptor (KAR) ^[2]. Associated diseases include neurodevelopmental and psychiatric disorders such as epilepsy (especially febrile seizures), schizophrenia, and Alzheimer's disease. Furthermore, SEZ6 overexpression has been detected in various high-grade neuroendocrine malignancies (e.g., small cell lung cancer (SCLC), medullary thyroid carcinomas), making it a novel therapeutic target in cancer ^[1].

The B6-hSEZ6 mouse is a humanized model constructed by gene-editing technology, in which the p.20 to partial intron 3 of mouse Sez6 is replaced with Human-Mouse chimeric CDS (Human SEZ6 Extracellular + Mouse Sez6 Intracellular)-3'UTR of Mouse Sez6-WPRE-BGH pA cassette. The murine signal peptide is remained. This model can be used for the research of the pathological mechanisms of neurodevelopmental and psychiatric disorders such as epilepsy (especially febrile seizures), schizophrenia, and Alzheimer's disease, and some cancers, as well as the development of relevant treatment methods, and the screening, development, and pre-clinical evaluation of SEZ6-targeted drugs.