Construction method and application of transgenic animal with blood-brain barrier permeability enhanced

Abstract

The invention discloses a construction method and an application of a transgenic mouse with blood-brain barrier permeability enhanced. The construction method of the transgenic mouse with blood-brain barrier permeability enhanced comprises the step of modifying genes of a mouse, so that expression quantity of slit protein is increased, and a transgenic animal model with blood-brain barrier permeability enhanced is obtained; Study shows that overexpression of slit protein can cause that a tricorn of the mouse is enlarged, a choroid plexus structure is seriously destroyed, and tight junction of epithelium cells is lost; observation on a vascular structure of the brain of a Slit-Tg mouse by virtue of immunofluorescent staining shows that bifurcation of blood vessels of the brain of the Slit-Tg mouse is less, more microvessels exist, the shapes of vessels are incomplete and the distribution of the vessels is irregular; a transmission electron microscope map also shows that endothelial cells of the Slit-Tg mouse are damaged and highly irregular and basement membranes of vessels are incomplete. Evansblueassay detects that the permeability of the mouse is enhanced, i.e., the detection result shows that the blood-brain barrier permeability of the Slit-Tg mouse is enhanced, the Slit-Tg mouse can be applied to an animal experiment of central nervous system drugs and the Slit-Tg mouse can be used for screening, research and development as well as therapeutic effect evaluation on nervous system drugs.

Description

Technical field [0001] The present invention involves the construction method and application of a genetically modified animal model, and specially involves the construction method and application of a genetically modified animal model with increased permeability of the blood -brain barrier. Background technique [0002] The central nervous system is the strictest and sensitive system of the human body.Normal nerve function requires a highly strict extracellular environment. The concentration of sodium, calcium, and potassium needs to be limited to a very narrow range.In addition, the metabolic demand of the nervous system is very strong, and its consumption of 20%of human oxygen consumption. [0003] The nervous system is very sensitive to many chemicals. Many of the substances in daily diet, although it has no harm to other organs, is neurotoxic, so there is a interface between the peripheral circulation system and the central nervous system of the mammalian body., To dynamical...

AI Technical Summary

Problems solved by technology

[0013] Studies have shown that in the treatment of intracranial diseases, focused ultrasound can not only ablate the blood-brain barrier, but also partially open the blood-brain barrier, but it still cannot open the blood-brain barrier stably.

[0014] Although there are many ways to open the blood-brain barrier at present, there are problems in varying degrees, such as safety, targeting, tissue compatibility, etc., which seriously restrict the development of central nervous system drugs.

Images