Effects of CTNND2 knockout on cerebellar development and motor function in mice
10.16098/j.issn.0529-1356.2021.04.004
- Author:
Lu-Yi WANG
1
;
Man XU
1
;
Ying-Bo LI
1
;
Bo-Yi TANG
2
;
Jiang-Hang WANG
2
;
Yu-Yin WANG
2
;
Le-Jing XIE
2
;
Xiao-Yue ZHANG
3
Author Information
1. Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University
2. Medical Imaging and Clinical Medicine, The Second Clinical Medical College, Chongqing Medical University
3. Clinical Medicine, The First Clinical Medical College, Chongqing Medical University
- Publication Type:Journal Article
- Keywords:
Cerebellum;
CTNND2;
Gene knockout;
Golgi staining;
Immunofluorescence staining;
Motor function;
Mouse;
Purkinje cell
- From:
Acta Anatomica Sinica
2021;52(4):520-527
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of CTNND2 knockout on cerebellar neuronal development and motor function in mice, as well as its possible mechanisms. Methods The mice were divided into two groups (n = 10 in each group), all of them were 7 weeks old : wild-type (WT) C57BL/6J mice were treated as control group, and homozygous of CTNND2 knockout (CTNND2 7) mice were treated as experimental group, the genotype of CTNND2 7 mice were detected with PCR. The motor function of two groups were detected by beam walking test, hanging wire test and gait analysis test. The changes of cerebellar Purkinje cells were detected by immunofluorescence staining and Golgi staining. Western blotting was performed to detect the expression levels of synapse-associated proteins phosphorylated synapsin 1 (p-Synl), synapsin 1 (Synl), ELKS and postsynaptic density protein 95(PSD95), as well as phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and mammalian target of rapamycin (mTOR). Results Compared with the WT mice, except the increase in time to traverse the beam, there was a decrease in the proportion of pass on the beam, or latency to fall from the hanging wire, or score of hanging wire, or fore-stride length and hind-stride length of CTNND2 7 mice. There was also a decrease in numbers of Purkinje cells and its dendritic arborization in cerebellum of CTNND2 7 mice. The ratio of p-Synl/ Synl, p-Akt/Akt and p-mTOR/mTOR, as well as the expression levels of ELKS, PSD95 and PI3K were lower than those of WT mice. Conclusion CTNND2 knockout can affect the number and dendritic architecture of Purkinje cells, as well as synthesis of synapse-associated proteins in cerebellum by down-regulating PI3K/Akt/mT0R signaling pathway, resulting in cerebellar developmental disorder, thereby affecting motor function of mice.
