Method for screening PTPzeta activity promoter or inhibitor

a promoter or inhibitor technology, applied in the direction of nervous disorders, drug compositions, instruments, etc., can solve the problem that the physiological role of ptp has been hardly elucidated so far

Inactive Publication Date: 2007-04-05
JAPAN SCI & TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the physiological role of PTPζ has been hardly elucidated so far.

Method used

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  • Method for screening PTPzeta activity promoter or inhibitor
  • Method for screening PTPzeta activity promoter or inhibitor
  • Method for screening PTPzeta activity promoter or inhibitor

Examples

Experimental program
Comparison scheme
Effect test

example 1

Physiological Role of PTPζ In Central Dopamide Pathway and Monoanine Pathway, and Usefulness of a PTPζ-Deficient Mouse

[0031] Though large amount of PTPζ is expressed in the central nervous system, its neurophysiologic role has been unknown. Therefore, the importance of PTPζ molecule in higher cerebral function was examined at individual level by comparing and analyzing a PTPζ gene-deficient mouse and a wild-type mouse behaviorally and neuropharmacologically.

example 1-1

Method

(A-1 Animals)

[0032] A PTPζ-deficient mouse was generated by the method described in the aforementioned paper written by the present inventors (Neuroscience Letters 274, 135-138, 1998). A LacZ gene was inserted into the position immediately after the translation initiation codon in exon 1 of a PTPζ gene of a mutant mouse and accordingly, a LacZ gene was expressed under the control of expression regulatory unit of the PTPζ gene. In this experiment, a knockout mouse was backcrossed with inbred C57BL / 6J line for 4 generations, and male littermates of 2 to 5 months old were used. The animals were housed in an animal care facility at 25.degrees C., with a 12 / 12 hours light-dark cycle and fed food and water ad libitum. Animals were cared in accordance with the institutional guidelines.

(A-2 Behavioral Experiment)

[0033] A behavioral experiment was conducted during the light cycle from 7:00 a.m. to 7:00 p.m.

A-2-1

[0034] In an open field test, a mouse was placed in the center of ...

example 1-2

Results

(Behavioral Phenotype of PTPζ-Deficient Mice)

[0046] In order to elucidate the behavioral phenotype of PTPζ-deficient mice, behavioral observation was conducted by an open field test (the above-mentioned methods A-1 and A-2-1). Locomotor activity (A) and rearing (B) of wild-type mice (PTPζ+ / +, n=10) and PTPζ-deficient mice (PTPζ− / −, n=12) were measured for consecutive 2 days by the open field test, and the results are shown in FIGS. 1A and 1B, respectively. The data are presented as mean±SEM (*p<0.05). As a result, PTPζ-deficient mice exhibited larger amount of locomotor activity than wild-type mice, and significantly high motility in the open field on the first day. However, 24 hours later, the change disappeared in the test (FIG. 1A). On the other hand, significant change was not found in values for rearing, an exploration behavior (FIG. 1B). It was revealed that the PTPζ-deficient mice increased their responsibility of locomotor activity to novel circumstances.

[0047] Lo...

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Abstract

An object of the present invention is to provide a remedy for dysfunction of central monoamine pathway, a method for screening a PTPζ inhibitor or activator, which is useful as a remedy for gastric ulcer caused by Helicobacter pylori or pleiotrophin which is a heparin-binding secretory protein, and a non-human model animal being hyposensitive to a stimulant drug, VacA which is a toxin of Helicobacter pylori, or pleiotrophin by utilizing the physiological function of PTPζ. After administering a subject material to PTPζ knockout mice and wild-type mice, PTPζ activity in the PTPζ knockout mice and the wild-type mice is compared and evaluated to screen a PTPζ inhibitor or activator. Examples of the comparison and the evaluation of the PTPζ activity include the comparison and the evaluation of the function of central monoamine pathway such as changes in the level of central monoamine metabolism, sensitivity to a stimulant drug, the presence of dysfunction of mesolimbic dopamine pathway, level of acclimation to new circumstances, or stress-responsiveness, and the comparison and the evaluation of the level of binding to VacA, a toxin of Helicobacter pylori, or pleiotrophin.

Description

TECHNICAL FIELD [0001] The present invention relates to a remedy for dysfunction of central monoamine pathway with the use of a non-human animal such as a mouse or the like which is generated by a homologous recombination technique for genes and is deficient in its receptor-type protein tyrosine phosphatase (PTPζ / RPTPβ) gene, a screening of a remedy for gastric ulcer caused by Helicobacter pylori or the like, a non-human model animal being hyposensitive to a central stimulant drug (an addictive drug) and a non-human model animal being hyposensitive to VacA, a toxin of Helicobacter pylori, or the like. BACKGROUND ART [0002] When a cell receives a stimulus from outside, its intracellular signaling pathway is activated to induce proliferation, differentiation, apoptosis and the like of the cell. Tyrosine phosphorylation of intracellular proteins acts an extremely important role in various phases of the signaling pathway, and the state of tyrosine phosphorylation of each protein is alwa...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A01K67/027A61P1/04A61P25/00C12N9/16C12N15/85C12Q1/42G01N33/50G01N33/68
CPCA01K67/0276A01K2217/075A01K2227/105A01K2267/03A01K2267/0356A01K2267/0368A01K2267/0393C12N9/16C12N15/8509C12Q1/42G01N33/5088G01N33/68G01N2333/205A61P1/04A61P25/00A61P43/00
Inventor NODA, MASAHARUFUJIKAWA, AKIHIRO
Owner JAPAN SCI & TECH CORP
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