These human Thy-1-COX-2 transgenic mice have expression of human COX-2 (PTGS2 or PGE2) directed primarily to neurons of the amygdala, striatum, cerebral cortex, and hippocampus by the murine Thy1.2 expression cassette. These mice may be useful to model chronic elevations in COX-2 enzymatic activity associated with neurodegenerative diseases and aging, oxidative metabolism of endocannabinoids in modulation of synaptic transmission and plasticity, and ischemia and postischemic inflammatory reaction.
Katrin I Andreasson, Stanford University
Mice hemizygous for the human Thy-1-COX-2 transgene (hCOX-2 transgene) are viable and fertile, with expression of human COX-2 (PTGS2 or PGE2) directed primarily to neurons of the amygdala, striatum, cerebral cortex, and hippocampus by the murine Thy1.2 expression cassette. These moderate overexpressing C57BL/6J COX-2 transgenic line 300 mice have PGE2 levels that are ~10-12-fold greater than non-transgenic controls (compared to ~25-40-fold overexpression in line 303; see Stock No. 010703). At approximately 12 months of age, COX-2 transgenic mice develop an age-dependent deficit in spatial memory. Around 20 months of age, a less pronounced, but significant deterioration in performance of non-spatial memory tasks develops. Further progressive memory impairments are observed over time. These cognitive deficits are associated with parallel age-dependent increases in cortical neuronal apoptosis and glial activation. Transgenic mice exhibit enhanced hippocampal longterm synaptic plasticity. Chronic overexpression of neuronal COX-2 enzymatic activity leads to long-term cellular changes that result in diminished neuron viability in transient focal ischemia/ischemic injury challenge. Elevated expression of COX-2 leads to increased oxidative degradation of endocannabinoids (eCBs); resulting in abolished depolarization-induced suppression of inhibition (DSI; or eCB-induced suppression of GABAergic synaptic transmission). These human Thy-1-COX-2 transgenic mice may be useful to model chronic elevations in COX-2 enzymatic activity associated with neurodegenerative diseases and aging, oxidative metabolism of endocannabinoids in modulation of synaptic transmission and plasticity, and ischemia and postischemic inflammatory reaction.
The human Thy-1-COX-2 transgene (hCOX-2 transgene) was designed with the entire 1.8 kb human COX-2 (PTGS2; prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) or PGE2) open reading frame sequence inserted into the 8.2 kb Thy-1 expression cassette (in the second exon of the "murine Thy-1.2 gene"). This transgene was injected into the male pronucleus of C57BL/6J cells. Transgenic founders were bred with C57BL/6J and mice from founder line 300 were found to have an approximately 10-12-fold increase in PGE2 expression. Transgenic mice were bred with C57BL/6NCrl mice for approximately five years prior to sending to The Jackson Laboratory Repository. Upon arrival, sperm from transgenic mice was cryopreserved. When rederiving the live colony, transgenic sperm will be used to fertilize oocytes from C57BL/6NJ females (Stock No. 005304).
|Expressed Gene||PTGS2, prostaglandin-endoperoxide synthase 2, human|
|Site of Expression|
|Allele Name||transgene insertion 300, Katrin Andreasson|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Allele Synonym(s)||Thy-1-COX-2 tg line 300; hCOX-2 tg|
|Gene Symbol and Name||Tg(Thy1-PTGS2)300Kand, transgene insertion 300, Katrin Andreasson|
|Gene Synonym(s)||Thy-1-COX-2 tg line 300; hCOX-2 tg|
|Promoter||Thy1, thymus cell antigen 1, theta, mouse, laboratory|
|Expressed Gene||PTGS2, prostaglandin-endoperoxide synthase 2, human|
|Strain of Origin||C57BL/6J|
|Molecular Note||The transgene construct contains the entire 1.8 kb human COX-2 (PTGS2; prostaglandin-endoperoxide synthase 2 or PGE2) open reading frame sequence inserted into the 8.2 kb Thy-1 expression cassette. This construct was injected into the male pronuclei of C57BL/6J cells. No founder lines were provided in the original reference but lines 300, 303, and 316 were characterized in subsequent publications. Mice from founder line 300 were found to have an approximately 10-12-fold increase in PGE2 expression.|
|Mutations Made By|| |
Katrin Andreasson, Stanford University
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"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.