Expression of protein tyrosine kinase 7 and receptor tyrosine kinase-like orphan receptor 2 in the brainstem of amyotrophic lateral sclerosis transgenic mice with hSODl-G93A mutation
10.16098/j.issn.0529-1356.2022.06.001
- Author:
Fan-Di MENG
1
;
Ying-Jun GUAN
1
;
Zhen-Han ZHAO
1
;
Yan-Chun CHEN
1
;
Jin-Meng LIU
1
;
Xue-Mei WANG
1
;
Fan-Di MENG
2
;
Ying-Jun GUAN
2
;
Zhen-Han ZHAO
2
;
Yan-Chun CHEN
2
;
Jin-Meng LIU
2
;
Xue-Mei WANG
2
;
Hao-Yun ZHANG
2
;
Feng-Hua ZHOU
2
Author Information
1. Histology and Embryology Department
2. Laboratory of Neurologic Disorders and Regenerative Repair, Weifang Medical University
- Publication Type:Journal Article
- Keywords:
Amyotrophic lateral sclerosis;
Brainstem;
Immunofluorescence;
Protein tyrosine kinase 7;
Receptor tyrosine kinase-like orphan receptor 2;
Transgenic mouse
- From:
Acta Anatomica Sinica
2022;53(6):689-697
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the relationship between changes in protein tyrosine kinase 7 (PTK7) and receptor tyrosine kinase-like orphan receptor 2 ( ROR2) expression in the brainstem and the pathogenesis of amyotrophic lateral sclerosis (ALS). Methods Forty-four human superoxide dismutase 1( hSODl)-G93A mutant ALS transgenic mice were selected, and an equal number of wild-type littermates was used as control. The brainstems were isolated at da)' 70, day 95, day 108 and da)' 122 after birth, and the morphology of frypoglossal nucleus (12N) and nucleus of facial nerve(7N) neurons in the brainstem of the model mice were observed by Nissl staining. The mRNA and protein expression of PTK7 and ROR2 were detected by RT-PCR and Western blotting respectively, and the cellular localization and distribution of PTK7 and ROR2 in 12N and 7N were observed by immunofluorescence double-labeling technique. Results The result of Nissl staining showed that Nissl bodies in the neurons reduced distinctly with vacuolar degeneration of neurons, cell body atrophy and nuclear volume reduction in the 12N and 7N brainstems of ALS transgenic mice. RT-PCR result indicated that ROR2 and PTK7 mRNA level in the brainstem of ALS transgenic mice were up-regulated at da)' 70, da)' 95, day 108 and day 122 compared with wild-type littermates. Western blotting result showed that PTK7 protein was up-regulated at day 70, day 95, day 108 and day 122, ROR2 protein was up-regulated at day 70, day 95, day 108, and down-regulated at day 122 in the brainstem of ALS transgenic mice compared with wild-type littermates. Immunofluorescence result showed that ROR2/neuronal nuclei (NeuN)and PTK7/NeuN double positive cells, ROR2/glial fibrillary acidic protein (GFAP) and PTK7/GFAP double positive cells were observed in the 12N and 7N of the brainstem of ALS transgenic mice and wild-type mice, suggesting that ROR2 and PTK7 were expressed both in neurons and astrocytes. Conclusion PTK7 and ROR2 are abnormally expressed in the brainstem of ALS transgenic mice, which is closely related to the pathogenesis of ALS.
