B6.Cg-Tg(tetO-DRD2)2-5Kndl/J

Stock number: 028294
Product name: tetO-D2R
Strain synonyms: tetO_hD2-5
Research areas: Neurobiology Research, Research Tools

Description

The human dopamine receptor D2 is conditionally expressed under the regulatory control of the tetO promoter in these tetO-D2R mice. When combined with a tTA allele, overexpression of DRD2 can be directed to tissues/cells of interest. Administration of doxycycline blocks expression of DRD2.

Detailed description

Increased activity of D2 receptors (D2Rs) in the striatum has been linked to the pathophysiology of schizophrenia. These transgenic mice express increased levels of the human DRD2 (dopamine receptor D2) gene under the regulatory control of a tetO promoter.

When crossed with Camk2a-tTA mice (e.g. Stock No. 003010), expression of DRD2 is restricted to the striatum in a reversible manner. Compound transgenic mice exhibit selective cognitive impairments in working memory tasks and behavioral flexibility without more general cognitive deficits. The deficit in the working memory task persists even after the transgene has been switched off through the administration of doxycycline, indicating that it results not from continued overexpression of D2Rs but from excess expression during development.

Development

The tetO promoter, consisting of seven operator sequences of the E. coli Tn10 teteracycline resistance operon and a Cytomegalovirus (CMV) minimal promoter, drives expression on the human DRD2 (D2R) gene and hGHpA (2.1 kb of the human growth hormone gene harboring the hGH polyadenlyation signal). The transgenic vector was injected into B6CBAF2 blastocysts. Resultant mice were backcrossed to C57BL/6J for more than 20 generations by the donating lab.

Allele

Symbol: Tg(tetO-DRD2)2-5Kndl
Name: transgene insertion 2-5, Eric R Kandel
MGI accession ID: MGI:5693386
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence
Marker symbol: Tg(tetO-DRD2)2-5Kndl
Marker name: transgene insertion 2-5, Eric R Kandel
Chromosome: UN
Strain of origin: (C57BL/6 x CBA)F2
Expressed genes: DRD2,dopamine receptor D2,human
Molecular note: The tetO promoter, consisting of seven operator sequences of the E. coli Tn10 tetracycline resistance operon and a Cytomegalovirus (CMV) minimal promoter, drives expression on the human DRD2 (D2R) gene and hGHpA (2.1 kb of the human growth hormone gene harboring the hGH polyadenylation signal).