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Construction method of insufficiency of myelination and myelination aplastic disorder animal model

A construction method and animal model technology, applied in the field of biomedicine, can solve problems such as unreported applications and unclear effects

Active Publication Date: 2022-05-17
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of c-Abl in OL lineage cells is unclear, and its application in the construction of myelin-related disease models has not been reported

Method used

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  • Construction method of insufficiency of myelination and myelination aplastic disorder animal model
  • Construction method of insufficiency of myelination and myelination aplastic disorder animal model
  • Construction method of insufficiency of myelination and myelination aplastic disorder animal model

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Effect of embodiment 1c-Abl gene knockout on myelin sheath development

[0062] 1. Method

[0063] 1. Experimental animals

[0064] C57BL / 6 male mice (8-10 weeks old) were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. (Beijing, China). c-Abl f / f Mice (donated by Professor Cang Yong from the Institute of Life Sciences, Zhejiang University) were crossed with Olig2-Cre mice (gifted by Professor Xiao Bo, Department of Biology, Southern University of Science and Technology) to obtain OL lineage-specific knockout c-Abl mice . male offspring c-Abl f / f ; Olig2-Cre (c-Abl conditional knockout [c-Abl CKO]) and c-Abl f / f (wild type [WT]) was used for experiments. Mice were maintained on a 12:12h light-dark cycle with adequate food and water. All experiments used male mice to avoid the influence of gender in behavioral tests, and the experimental protocol was approved by the Experimental Animal Ethics Committee of Beijing Institute of Basic Me...

Embodiment 2c

[0078] Effect of Example 2c-Abl knockout on remyelination in vivo

[0079] 1. Method

[0080] 1. Cuprizone (CPZ)-induced mouse demyelination model

[0081] Take 8-week-old male C57BL / 6 mice, grind them into powder with 0.2% (w / w) CPZ (China, Meilun Biology), mix them into animal feed, and feed them for 6 weeks to induce demyelination. Stopping the CPZ diet allowed for myelin regeneration. Experimental animals (0, 2, 4 weeks after CPZ diet) were anesthetized and perfused with normal saline intracardiacly. The brain tissues of the animals were taken, fixed with paraformaldehyde at 4°C for 24 hours, dehydrated with sucrose gradient, and cut into 40 μm thick brain slices for further analysis.

[0082] 2. Open field experiment

[0083] The open field apparatus is a square box (50cm x 50cm x 20cm) used to analyze spontaneous activity in mice. Mice were placed in the open field (wiped clean with 75% ethanol solution) and allowed to explore the box freely for 5 minutes. Velocity...

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Abstract

The invention discloses a construction method of an animal model with insufficiency of myelination and myelination aplastic disorder. The research proves that the knockout of c-Abl can cause insufficient myelin sheath formation of mice and delay of myelin sheath regeneration of mice to cause obstacles, and on the basis of the research results, an animal model with insufficient myelin sheath formation and myelin sheath regeneration obstacles can be constructed by knocking out c-Abl, so that a research basis is provided for researching a myelin sheath formation mechanism.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a method for constructing animal models of insufficient myelin sheath formation and myelin sheath regeneration disorder. Background technique [0002] Axonal myelination is critical for the rapid propagation of action potentials during the regulation of information flow within neural circuits; moreover, myelin provides metabolic and nutritional support to axons to prevent their pathology. Therefore, hypomyelination or dysmyelination in the central nervous system (CNS) greatly affects the realization of brain function, manifested as hypomyelination, leukodystrophy, multiple sclerosis (MS), neurodegeneration and other diseases. [0003] Oligodendrocytes (OLs) are responsible for myelination in the central nervous system. During development, oligodendrocyte precursor cells (OPCs)—specifically expressing glial cell antigen 2 (NG2) and platelet-derived growth factor receptor α (PDGFRα)— migr...

Claims

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Application Information

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IPC IPC(8): A01K67/027C12N15/54A61K49/00
CPCA01K67/0276C12N9/12A61K49/0008C12Y207/10A01K2217/075A01K2217/15A01K2227/105A01K2267/0318A01K2207/20A01K2217/206
Inventor 袁增强王树坤张峻孙建广吴荣张莹
Owner ACADEMY OF MILITARY MEDICAL SCI
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