General Information

Transgene: 1950-bp HindIII cDNA fragment containing human cyclooxygenase-2 (hCOX-2) coding region

Promoter: rat neuron specific enolase (NSE) promoter, including 2600 bp segment of promoter and 5' flanking region, as well as exon 1, intron1, and 6 bp of exon 2 of rat NSE gene.

Mouse Strain: C57B1/6 x C3H (B6C3) F1 hybrid

Phenotype

Neuropathological Analysis:

NSE promoter-driven overexpression produced high levels of hCOX-2 in parietal cortex, pyramidal CA3-CA1 layers and dentate gyrus granule cell layers of hippocampus, thalamus, cerebellar Purkinje cell layer, as assessed by in situ hybridization with an antisense probe and quantitative X-ray film autoradiography.

Relative to endogenous mouse (m) COX-2 mRNA, hCOX-2 mRNA was elevated 3- to 4-fold in parietal cortex, pyramidal CA3-CA1 layers and dentate gyrus granule cell layers of hippocampus, and thalamus.

In a study of kainic acid-induced seizures, intensity of seizures, as well lethality, was markedly increased in hCOX-2 mice relative to wild-type controls. There was also increased expression of the immediate early genes c-fos and zif-268.

In a study by Speilman et al. (2002), and relative to wild-type controls, hCOX-2 mouse were found to have a two-fold increase in brain prostaglandin E[2]. There was also a significant increase in mRNA for the complement component C1qB (but not C3 or C4) in hippocampal pyramidal neurons and in the dentate gyrus. This latter increase was partially prevented by the COX-2-selective inhibitor nimesulide.

Availability

Patents:

References

Primary:

Kelley KA, Ho L, Winger D, Freire-Moar J, Blanco Borelli Cy, Aisen PS, Pasinetti GM. Potentiation of excitotoxicity in transgenic mice overexpressing neuronal cyclooxygenase-2. Am J Pathol. 1999 Sep 3;155(3):995-1004. Abstract

Xiang Z, Ho L, Valdellon J, Borchelt D, Kelley K, Spielman L, Aisen PS, Pasinetti GM. Cyclooxygenase (COX)-2 and cell cycle activity in a transgenic mouse model of Alzheimer's disease neuropathology. Neurobiol Aging 2002 May-Jun;23(3):327-34. Abstract .

Secondary:

Spielman L, Winger D, Ho L, Aisen PS, Shohami E, Pasinetti GM. Induction of the complement component C1qB in the brain of transgenic mice with neuronal overexpression of human cyclooxygenase-2. Acta Neuropathol. 2002;103:157-62. Abstract