Application of gama-aminobutyric acid (GABA) translocator isoform I gene knockout mouse system in building novel drug induced epilepsy animal model

An epilepsy animal, gene knockout technology, applied in gene therapy, pharmaceutical formulations, genetic material components, etc., can solve the problems of easy death induction effect between individuals, low induction success rate, low epilepsy grade and other problems, to achieve epilepsy susceptibility Increased effect, high induction success rate, high epilepsy grade

Inactive Publication Date: 2016-06-22
JINSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, normal mice are often used to induce epilepsy with drugs to establish animal models of epilepsy. However, there are defects such as low induction success rate, low epilepsy grade, unstable state, easy death, and large differences between individuals in the induction effect of the same batch. Serious hinder the progress of related scientific research
[0008] There are no related reports on the establishment of epilepsy animal models using GAT1 gene knockout mice

Method used

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  • Application of gama-aminobutyric acid (GABA) translocator isoform I gene knockout mouse system in building novel drug induced epilepsy animal model
  • Application of gama-aminobutyric acid (GABA) translocator isoform I gene knockout mouse system in building novel drug induced epilepsy animal model
  • Application of gama-aminobutyric acid (GABA) translocator isoform I gene knockout mouse system in building novel drug induced epilepsy animal model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] 1. Materials

[0025] 1.1 Experimental animals

[0026] A total of 30 mice, all male. Among them, 15 GAT1 knockout mice and 15 C57 wild-type mice were purchased from Shanghai Southern Model Organism Research Center. The name of the GAT1 knockout mouse strain: B6.129-Slc6a1 tm1Srcmo , strain number: NM-KO-00002, knockout GAT1 gene NCBI number: 232333. Using the random grouping method, the weight of the mice in each group was comparable, and the specific grouping conditions were as follows:

[0027] 1) Normal saline control group (Control, n=14), including:

[0028] ①Wild-type control (wt-Con, n=7): only an equal volume of saline was injected intraperitoneally;

[0029] ② Genotype control (GAT1-Con, n=7): only an equal volume of normal saline was injected intraperitoneally.

[0030] 2) Epilepsy model group (Model, n=16), including:

[0031] ①Wild-type model (wt-Model, n=8): intraperitoneal injection of PTZ, 30mg / kg body weight;

[0032] ② Genotype model (GAT1-Model...

Embodiment 2

[0064] To investigate the reproducibility of the epilepsy model using GAT1 knockout mice. Divided into 3 batches, each batch of 10 GAT1 gene knockout mice, using the method described in Example 1 to prepare epilepsy models. The death rate and induction success rate of each batch of mice after modeling, the grade of epileptic seizures after the last intraperitoneal injection, and the total power of EEG of mice after modeling were counted.

[0065] Table 4 shows the statistical results of mouse mortality and induction success rate after each batch of modeling.

[0066] Table 4 Mouse mortality rate and induction success rate after modeling in each batch

[0067]

[0068] Table 5 shows the statistical results of the seizure levels of the last injection of mice after each batch of modeling.

[0069] Table 5 The number of samples of each batch of mice after intraperitoneal injection according to the behavioral grade of epileptic seizures

[0070]

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Abstract

The invention relates to application of a gama-aminobutyric acid (GABA) translocator isoform I gene knockout mouse system in building a novel drug induced epilepsy animal model. According to the invention, a GAT1 gene knockout mouse is adopted to build an animal epilepsy model, the effect is compared with modeling by adopting wild type mice, and the method provided by the invention is proved to be with high success rate, high epilepsy level, stable state, difficulty in death and good repeatability, and can well meet the requirement of epileptic disease research. The result provided by the invention also proves that after GAT1 gene knockout, the mouse epilepsy susceptibility is increased, the GAT1 gene or protein can be used as a therapeutic target for epilepsy, and the level of the GAT1 gene or protein can be used as a biomarker for epilepsy diagnosis.

Description

technical field [0001] The invention relates to the establishment of animal models, in particular to the establishment of novel drug-induced epilepsy animal models using gamma-aminobutyric acid transporter subtype I gene knockout mouse lines. Background technique [0002] Epilepsy, commonly known as "shorn wind" or "epilepsy", is a chronic disease in which the sudden abnormal discharge of brain neurons leads to transient brain dysfunction. According to the latest epidemiological data in China, the overall prevalence rate of epilepsy in China is 7.0‰, the annual incidence rate is 28.8 / 100,000, and the prevalence rate of active epilepsy with seizures within one year is 4.6‰. Based on this, it is estimated that there are about 9 million epilepsy patients in China, of which 5 to 6 million are active epilepsy patients, and about 400,000 new epilepsy patients are added every year. In China, epilepsy has become the second most common disease in neurology after headache. sick. [...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/55A61K49/00A61K48/00A61K45/00A01K67/027
CPCA01K67/0276A01K2217/075A01K2227/105A01K2227/106A01K2267/0356A61K31/55A61K45/00A61K48/00A61K49/0004A61K49/0008
Inventor 陈英辉李炳邵一叶陈龙罗琼冯永浩谢阳梅
Owner JINSHAN HOSPITAL FUDAN UNIV
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