动物造模,药效评价,基因敲除癫癎 z-bio 2024-08-21 395

　　(1) The replication methods mainly use gene knockout and transgenic techniques to replicate the model.

　　(2) Model features

　　1) Tottere mouse model (TG/TG series): TG/TG is one of the most extensively studied genetic epilepsy models. Apart from ataxia, it mainly manifests as absence like seizures and bilateral synchronous 6-7 Hz spike waves and multi spike slow waves. The onset occurs at around 4 weeks of age, and its susceptibility is believed to be related to excessive control of norepinephrine in the brain. Recently, it has been discovered that this type of mouse has a gene mutation encoding the alpha 1 subunit calcium channel, which is believed to be related to its susceptibility to seizures. This model can be used for the study of the mechanism of epilepsy caused by gene mutations.

　　2) Gene knockout and transgenic mouse models: The first homozygous mouse model was the Cystatin B gene knockout mouse model for myoclonic epilepsy (PME) syndrome. The Cystatin B gene encodes an inhibitor of Cystatin protein kinase, Cystatin B. Knocking out the gene prevents the expression of Cystatin B, and U-L PME patients have mutations and functional deletions in this gene. There is a special overlap in the neural phenotype between cystatin knockout mice and U-L type PME patients. Ionic channel diseases in the central nervous system are associated with human epilepsy, such as the Sharker type delayed rectifier potassium channel gene knockout mouse model, which exhibits severe tonic clonic seizures and is prone to early death. The transgenic Q54 mouse model showed that epileptic seizures in Q54 mice began at 2 months of age, accompanied by restricted behavior and rigid repetitive movements. Continuous EEG monitoring revealed localized epileptic activity in the hippocampus, even extending to the cortex. Pathological examination revealed significant cell loss and gliosis in the hippocampal CA1 to 3 and portal regions. Transgenic Q54 mice provided a genetic model in which SCN2A was found to be a candidate gene for human epilepsy.

　　(3) Comparative medicine epilepsy is an important neurological disease that requires the development of effective antiepileptic drugs. When designing and developing new anti epileptic drugs, animal epilepsy models must be utilized. Experimental animal models of epilepsy have similarities with human seizures, and their mechanisms are similar to the pathological and physiological states of human seizures. Therefore, choosing the appropriate animal model is crucial. These models can serve as preliminary screening tools to identify more targeted therapeutic drugs.