Model for neurodegenerative disease

A technology of transgenic animals and animals, applied in the field of neurodegenerative diseases, can solve the problem of knowing downstream intracellular effectors

Inactive Publication Date: 2007-12-05
CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC) +1
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Although activation of glycogen synthase kinase-3β (GSK-3β) has been suggested to be responsible for neuronal dysfunction, little is known about the downstream intracellular effectors responsible for this neuronal dysfunction

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Model for neurodegenerative disease
  • Model for neurodegenerative disease
  • Model for neurodegenerative disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0022] We preferentially used the tet-regulatory system in mice. This tet-regulatory system has been used for conditional gene expression in eukaryotic cell systems and in mice (Gingrich and Roder, 1998). By using this system to prime the transgenic expression of mutant types of huntingtin, some of us have recently established the first conditional animal models of neurodegenerative diseases (Yamamoto et al., 2000). The tet-regulatory system is particularly useful when mimicking pathological conditions, as it can be used to: prevent perinatal lethality due to transgene toxicity, initiate transgene expression only in adulthood, and once the associated phenotype changes That is, transgene expression is stopped (Kelz et al., 1999; Yamamoto et al., 2000).

[0023] Regulation of this system is achieved by tetracycline-regulated transactivator (tTA), a chimeric protein consisting of a tet-repressor DNA-binding domain and a VP16 transactivation domain ( Gossen and Bujard, 1992). T...

Embodiment

[0026] The present invention is further illustrated by the following examples of our experimental work. Generation of injection fragments

[0027]The 8.0 kb Ase I fragment (BitetO) was used for microinjection. To generate BitetO, the 1.5 kb Hind III fragment corresponding to the Xenopus GSK-3β cDNA with the N-terminal MYC epitope was excised from the pcDNA3-GSK3 plasmid (Sanchez et al., 2000). This fragment was subcloned into the pCRII cloning vector (Invitrogen) digested with Hind III. Digest with XhoI to test for correct orientation. Then, by Nsi I-Not I digestion, a 1.5 kb fragment was excised and subcloned into the Pst I-Not I site of a plasmid containing a bidirectional tetO sequence that was replaced by a giant lacZ reporter gene sequence. Cytovirus (CMV) minimal promoter flanking (pBI-3, (Baron et al., 1995)). Finally, the 8.0 kb Ase I BitetO fragment was microinjected into single-cell CBAxC57BL / 6 embryos. Founder mice were identified using PCR and confirmed by Sou...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

A transgenic animal in which GSK-3beta protein is over-expressed is useful as a model for neurodegenerative disease.

Description

[0001] The present invention relates to animal models for neurodegenerative diseases, in particular Alzheimer's disease. Background of the Invention [0002] Alzheimer's disease (AD), one of the most common neurodegenerative diseases in developed countries, is characterized by progressive memory loss and impairment of language and behavior, ultimately leading to death (Alzheimer, 1911; Yankner, 1996 ). Cognitive decline in AD is accompanied by neuronal atrophy and loss primarily in the cortex, hippocampus and tonsils (Gomez-Isla et al., 1997). In addition to a specific pattern of neuronal cell death, AD is also characterized by two neuropathological hallmarks: senile plaques and neurofibrillary tangles (NFTs). [0003] Senile plaques are extracellular deposits of amyloid fibrils composed of 39-43 amino acid beta-amyloid peptides (ABs) that are usually surrounded by dystrophic axons (Glenner and Wong, 2007). 1984; Masters et al., 1985; Selkoe, 1994). [0004] NFTs are collec...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/56A61K49/00A01K67/027C12N9/12C12N15/09C12N15/85
CPCC12N9/1205A01K2227/105A01K2217/20A01K2267/0318A01K2217/05A01K2267/0312A01K67/0275C12N15/8509A01K2217/00A01K2207/15A01K67/027
Inventor 费利克斯·埃尔南德斯·佩雷斯赫苏斯·阿维拉·德格拉多何塞·哈维尔·卢卡斯·洛萨诺
Owner CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC)
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap