14 December 2019 |       Share
 
 
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PPRE-Luc mouse model
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Introducing the repTOP™ PPRE-Luc model

“PPRE” is the PPAR-receptor  Responsive Element

Follow the webinar on Charles River web site.

PPAR (Peroxisome proliferator activated) α, β/δ and γ receptors are a class of nuclear receptors involved in the regulation of cellular metabolism. When activated, they bind to PPAR-responsive elements (PPRE) on gene promoters and activate transcription. The repTOP™ PPRE-Luc model produces luciferase under the control of a pan-PPAR receptor responsive element.


   SATURN Validation results:
Specificity: reporter specifically induced by Peroxisome Proliferator Activated Receptor (PPAR) ligands.
Accuracy: quantitative bioluminescence readout upon stimulation with pharmacological doses of selective agonists.
Turn-over: luciferase reporter half-life is 2.6 hours in all tissues.
Ubiquity: PPAR-regulated expression has been detected in all tissues known to express PPARs.
Reproducibility: typical inter-individual variability in acute treatments in the liver with PPARα/γ agonists (SEM: 15% in vivo; 10% ex vivo).
Non-invasive: suitable for in vivo optical imaging.

In the course of the SATURN validation process of PPRE-Luc repTOP™ mice, a commercial well-characterised inhibitor of PPARα(MK-886) was used for checking specificity of the reporter system. The drug effectively suppressed PPAR activity in most organs. Surprisingly, it acted as a pure inducer of the receptor in testis and lung. It is not uncommon for nuclear receptor modulators displaying a tissue-specific opposite activity. For MK-886 these findings would have prompted a thorough toxicological investigation to rule out possible deleterious side-effects in drug discovery and development.

repTOP™ PPRE-Luc  In Vivo Giude on Charles River web site
repTOP™ PPRE-Luc
technical sheet on Charles River web site

References

Application areas:

·         Diabetes

·         Arteriosclerosis

·         Inflammation

·         Lipid metabolism disorders

·         Cardiovascular diseases

·         Genetic diseases (e.g. X-linked adrenoleukodistrophy)

 

Upon request, TOP srl is able to offer also repTOP™ PPRE-Luc cells and vectors.

For inquiries, please contact business.development@top-mice.com

 

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