Method of screening PTPζ activity promoter or inhibitor
View Patent ↗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, and a non-human model animal being hyposensitive to a stimulant drug, 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.
1. A method for identifying a PTP-ζ inhibitor wherein a subject material is administered to a transgenic mouse whose genome comprises a homozygous disruption of the proteoglycan-type-receptor-type protein tyrosine phosphatase (PTP ζ) gene such that no PTP-ζ is expressed, wherein said mouse exhibits a dysfunction of the central monoamine pathway activity, and to a wild-type littermate mouse, and evaluating and comparing PTP ζ-related central monoamine pathway activities in the transgenic mouse and the wild-type mouse, wherein a decrease in central monoamine pathway activity in the wild-type mouse compared to that in the transgenic mouse is indicative of a subject material that is a PTP-ζ inhibitor.
2. The method for identifying a PTP-ζ inhibitor according to claim 1 , wherein the comparison and the evaluation of the function of the central monoamine pathway is the comparison and the evaluation of changes in the level of central monoamine metabolism, the sensitivity to a drug that stimulates the central monoamine pathway, the presence of dysfunction of the mesolimbic dopamine pathway, the level of acclimation to new circumstances, or stress responsiveness.
3. The method for identifying a PTP-ζ inhibitor according to claim 2 , wherein the mouse whose genome comprises a homozygous disruption of the PTP-ζ gene is backcrossed for 4 or more generations.