These human Thy-1-COX-2 transgenic mice express human COX-2 (PTGS2 or PGE2) primarily in neurons of the amygdala, striatum, cerebral cortex, and hippocampus as directed by the murine Thy1.2 expression cassette. These overexpressing COX-2 transgenic mice exhibit PGE2 levels that are ~25-40-fold greater than non-transgenic controls.
Katrin I Andreasson, Stanford UniversityRead More +
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 overexpressing C57BL/6J COX-2 transgenic line 303 mice have PGE2 levels that are ~25-40-fold greater than non-transgenic controls (compared to ~10-12-fold overexpression in line 300; see Stock No. 010800). 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 303 were found to have an approximately 25-40-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 303, Katrin Andreasson|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Allele Synonym(s)||Thy-1-COX-2 tg line 303; hCOX-2 tg|
|Gene Symbol and Name||Tg(Thy1-PTGS2)303Kand, transgene insertion 303, Katrin Andreasson|
|Gene Synonym(s)||Thy-1-COX-2 tg line 303; 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 303 were found to have an approximately 25-40-fold increase in PGE2 expression.|
|Mutations Made By|| |
Katrin Andreasson, Stanford University
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