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.
Eric R Kandel, Columbia University
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.
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.
|Expressed Gene||DRD2, dopamine receptor D2, human|
|Site of Expression|
|Allele Name||transgene insertion 2-5, Eric R Kandel|
|Allele Type||Transgenic (Inducible, Inserted expressed sequence)|
|Gene Symbol and Name||Tg(tetO-DRD2)2-5Kndl, transgene insertion 2-5, Eric R Kandel|
|Promoter||tetO, tet operator,|
|Expressed Gene||DRD2, dopamine receptor D2, human|
|Strain of Origin||(C57BL/6 x CBA)F2|
|Molecular Note||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).|
Hemizygotes are viable and fertile.
When using the tetO-D2R mouse strain in a publication, please cite the originating article(s) and include JAX stock #028294 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.