AAV vector-mediated Sall2 overexpression slowing disease progression in amyotrophic lateral sclerosis transgenic mice
10.16098/j.issn.0529-1356.2025.02.001
- VernacularTitle:AAV载体介导的Sall2过表达延缓肌萎缩侧索硬化症转基因小鼠疾病进展
- Author:
Xue ZHANG
1
;
Chen-Chen WANG
;
Xue-Shuai GAO
;
Xue BAI
;
Xue-Mei WANG
;
Jin-Meng LIU
;
Ying-Jun GUAN
;
Yan-Chun CHEN
Author Information
1. 山东第二医科大学组织学与胚胎学教研室,山东潍坊 261053;山东省高校神经疾病与再生修复实验室,山东潍坊 261053
- Keywords:
Amyotrophic lateral sclerosis;
Adeno-associated virus;
Sal-like gene 2;
Western blotting;
Transgenic mouse
- From:
Acta Anatomica Sinica
2025;56(2):127-135
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.
