huSCN2A Mouse

Epilepsy, a chronic neurological disorder, is diagnosed in an estimated 5 million individuals globally each year. An epileptic seizure may result in brief involuntary convulsions, occasionally accompanied by loss of consciousness and urinary incontinence. Patients with epilepsy often face additional physical complications and psychological disorders. The risk of premature death for patients with epilepsy can be tripled, with the highest rates observed in low- and middle-income countries and rural areas ^[1]. The etiology of epilepsy is multifactorial, encompassing structural, genetic, infectious, metabolic, and immune factors. With the advent of genetic testing in pediatric neurology, a genetic cause is believed to underlie more than half of pediatric epilepsy cases. Voltage-gated sodium ion channel genes, including SCN1A, SCN2A, SCN3A, and SCN8A, are implicated in epilepsy. Single nucleotide variations (SNVs) can result in either loss or gain of function of the affected ion channels, such as in the case of epileptic encephalopathies (DEEs) associated with SCN2A ^[2-4]。

The SCN2A gene, encoding the α2 subunit of the voltage-gated sodium channel (Nav1.2), is a significant contributor to epilepsy. Mutations in SCN2A are associated with various neurological disorders and are inherited in an autosomal dominant manner. Current epilepsy treatments primarily aim to reduce seizure likelihood rather than address the underlying disease process. Sodium channel blockers (SCBs) may effectively treat epilepsy caused by SCN2A mutations. The discovery of more epilepsy gene pathogenic factors enhances our understanding of the epileptogenic process and opens the possibility for targeted gene therapy ^[5]. The ASO drug elsunersen (PRAX-222), developed by Praxis Precision Medicines, has received Priority Medicines (PRIME) certification from the European Medicines Agency (EMA) for treating SCN2A gain-of-function (GoF) developmental epileptic encephalopathy (DEE) ^[6-9]. Considering the genetic differences between animals and humans, humanizing mouse genes can expedite the clinical stages of these treatments. This strain is a humanized model of the mouse Scn2a gene, useful for epilepsy research. The homozygous huSCN2A mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.