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Anti-Alzheimer's Transgenic Drosophila Model and Its Application in Drug Screening

A fruit fly and model technology, applied in the fields of medicine and biology, can solve problems that consume a lot of time and money, and affect research progress

Active Publication Date: 2011-12-07
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the transgenic mouse models used to study AD need to consume a lot of time and money, seriously affecting the progress of research

Method used

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  • Anti-Alzheimer's Transgenic Drosophila Model and Its Application in Drug Screening
  • Anti-Alzheimer's Transgenic Drosophila Model and Its Application in Drug Screening
  • Anti-Alzheimer's Transgenic Drosophila Model and Its Application in Drug Screening

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0205] Example 1: Obtaining stable double-trait Drosophila lines by crossing transgenic Drosophila

[0206] In this example, the fruit flies of the original transgenic fruit flies were crossed with the DB fruit flies respectively, and the offspring fruit flies with the transfer gene and the balancer screening marker were obtained, and the specific screening marker was screened to obtain the line preservation (F2 ). The F2 generation fruit flies of the two strains were crossed to obtain the second generation of fruit flies, and the impure and double transgenic fruit flies (F3) that can be stably inherited were obtained by screening two different balancers at the same time, and obtained through selfing for one generation Pure and instrumental double transgenic Drosophila (F4) models that can be used for mating to produce offspring Drosophila.

[0207] There are two kinds of tool double transgenic fruit flies (F3) obtained by continuous crossing, namely (APP / APP; BACE / BACE) and ...

Embodiment 2

[0224] Example 2: Identification of the Drosophila model

[0225] 1. Human APP protein and β-secretase protein expressed in Drosophila

[0226] The C-terminus of the human APP protein contains fragments of β-amyloid protein, such as figure 2 Indicated by the black area, two forms of β-amyloid, Aβ40 and Aβ42, are produced after cleavage by β-secretase and γ-secretase in vivo. In the transgenic Drosophila expressing UAS-APP, the inventors can detect two kinds of glycosylated APP ( figure 2 Lanes 11 and 15 in the upper figure of B), after co-expressing human BACE protein, the expression of high molecular weight glycosylated APP was significantly reduced. It shows that in Drosophila, human BACE secretase is easy to cut high molecular weight APP. At the same time, the C-terminal fragment of APP generated by β-secretase cleavage [β-C-terminal fragment (CTF)] ( figure 2 B upper panel lanes 1, 2 and 5, 6). In the low-expression UAS-Aβ1-1 and UAS-Aβ1-2 fruit flies, the high-exp...

Embodiment 3

[0230] Example 3: The neurotoxicity caused by the deposition of amyloid protein caused by APP cleavage to generate Aβ was verified by survival and behavior experiments, and the regulation of β-secretase plays an important role in protecting neurons.

[0231] The methods of survival and behavioral experiments used in this example are referenced in Dissecting the pathological effects of human A{beta}40 and A{beta}42 in Drosophila: A potential model for Alzheimer's disease (PNAS, 2004, Zhong Yi et al.) , the specific scheme is as follows:

[0232] The experimental fruit flies are as follows:

[0233] Wild type Drosophila (WT): elav c155 / CS (CS is common wild-type Drosophila, see the aforementioned PNAS, 2004, the literature of Zhong Yi et al.); AD Drosophila (Aβ): elav c155 / +(y); Aβ1 / +, elav c155 / +(y); Aβ2 / + (see the aforementioned PNAS, 2004, the literature of Zhong Yi et al.); AD / APP; BACE Drosophila (APP / +; BACE / +): prepared in Example 1; AD / APP ; DPsn-BACE Drosophila (...

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Abstract

The invention relates to establishment and application of a model for screening medicines for treating Alzheimer disease, and aims to provide a transgenic Dosophila melanogaster model for studying molecular pathway of pathogenesis progress of Alzheimer disease and drug screening. The invention obtains stable heritable novel Drosophila melanogaster variety by successive crossing of available transgenic Drosophila melanogaster. The novel disease model can simulate the in vivo generation and metabolism processes of major pathogenic genes of Alzheimer disease, and reproduce the pathogenesis process of the disease. The Drosophila melanogaster model provided by the invention is proven by a variety of indicators closely related to the symptoms of disease, including survive curve, mobility and learning and memory indexes and in vivo experiments, to be distinctly different from other Alzheimer disease Dosophila melanogaster models in all respects.

Description

technical field [0001] The invention belongs to the field of medicine and biology, in particular, the invention relates to a molecule for studying the shearing effect of Alzheimer's disease (AD) pathogenic gene APP in vivo and its product β-amyloid protein in the pathogenesis process Mechanism and novel Drosophila model for screening new drugs for the treatment of AD. technical background [0002] Alzheimer's disease (AD) is a degenerative disease of the central nervous system. In recent years, it has become the fourth largest killer after vascular disease, cancer and stroke. According to the statistics of the World Health Organization, the number of people suffering from Alzheimer's disease worldwide is estimated to be around 18 million. Alzheimer's disease patients are clinically characterized by comprehensive dementia such as memory impairment, aphasia, apraxia, agnosia, impairment of visuospatial skills, executive dysfunction, and personality and behavior changes. [...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/033C12N5/07C12N5/079C12Q1/02C12Q1/25A61K49/00
CPCA01K67/0339A01K2227/706A01K2217/15A01K2267/0312A61P25/00A61P25/28
Inventor 裴钢赵简刘佳
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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