Transgenic animal model of mood disorders

摘要

A non-human transgenic animal having a polynucleotide encoding a PTN polypeptide, which polynucleotide is operably linked to a promoter, wherein said transgenic animal has greater than wild-type expression of the PTN polypeptide in at least one brain region, as well as related vectors, methods of producing transgenic animals, in vitro and in vivo screening methods for potential therapeutic agents, and methods for treating and diagnosing neuropsychiatric illnesses, particularly anxiety and depression, are disclosed.

主权项

1. A transgenic mouse whose genome comprises a polynucleotide encoding a Pleiotrophin (PTN) polypeptide, which polynucleotide is operably linked to a neuron-specific promoter, wherein said transgenic mouse has greater than wild-type expression of the PTN polypeptide in at least one brain region, and wherein said neuron-specific promoter is selected from the group consisting of: a Thy1 gene promoter, Neuron specific enolase (NSE) gene promoter; Rhombotin I gene promoter; PGK gene promoter; Neurofilament Low (NF-L) gene promoter; dopamine beta-hydroxylase (DBH) gene promoter; and Synapsin-1 gene promoter, and wherein said transgenic mouse exhibits at least one behavior selected from the group consisting of reduced time spent in open arms of an elevated plus maze; reduced time in central area in an open-field test; reduced time in light in a light-dark box test; increased latency to feed in a Novelty Suppressed Feeding Test; increased immobility time in tail suspension test; and reduced sucrose intake in sucrose intake task.