14 August 2020 |       Share
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repTOP™ ERE-Luc mouse
repTOP™ PPRE-Luc mouse
repTOP™ mitoIRE mouse
repTOP™ Ubi-Luc2 mouse
repTOP™ Ube2g2-Luc2 mouse

Introducing the repTOP™mitoIRE model

The repTOP™mitoIRE mouse was developed in collaboration with IRE's scientists (Istituto Regina Elena).

repTOP™mitoIRE mouse to measure cell proliferation in vivo

Follow the webinar on Charles River web site.


Is your anticancer drug candidate blocking mitosis?

Using   luciferase   as   a   biomarker  for   proliferation      repTOP™ mitoIRE revolutionizes current methodologies to investigate anti-neoplastic drugs by:  

1. Early identification of tumor cells
2. Precise measurement of cancer cells in the growing tumor mass
3. Continuous monitoring of tumor growth and development of distal lesions
4. Immediate identification of cells resistant to the treatment 

With repTOP™ mitoIRE you may avoid grafting of exogenous cancer cells and study tumor formation and relapse in genetic and chemically induced cancer models. More reliable definition of drug efficacy is achieved by working with immunocompetent mice with autologous tumors.  

The figure shows a skin tumor induced by DMBA/TPA in the repTOP™ mitoIRE mouse. Tumor proliferation is monitored in space and time by bioluminescence. Tumor promoting activity of the compounds is measured (lower panel) long before the papilloma is visible.

In adult mice, intense proliferation occurs in specific body districts responsible for hematopoiesis (e.g. bone marrow in femur and sternum). This basal proliferative activity must not be affected by the treatment.

Any compound generally affecting cell proliferation also in non-transformed tissues is reducing luciferase activity in the repTOP™ mitoIRE mouse.

In vivo imaging of 5FU effects

The cytotoxic effects of acute treatment with 5-fluorouracil (5FU) on proliferating bone-marrow cells is well described in the scientific literature (e.g. Radley JM and Scurfield G, 1979; Darnowski JW et al. 1985). In this experiment,repTOP™ mitoIRE mice were treated with increasing doses of 5FU. Both by in vivo imaging (A) and ex vivo luciferase assay (B) it is possible to easily detect this effect comparing the luminescence produced at day 0, and 2 days after treatment in the sternum and in the femur.

By using the repTOP™ mitoIRE mouse model, and monitoring for instance these two body areas, it is possible to easily and readily measure unspecific and undesired effects of novel cytostatic compounds on healthy tissues.

Is your compound affecting proliferation in healthy tissues?

When testing a new compound it is important to investigate potential negative effects on physiological cell renewal in specific organs, e.g. bone marrow, spleen, gonads or during embryonic development.

Embryos of the repTOP™ mitoIRE mouse strain express high levels of luciferase in proliferating tissues, as assessed by ex-vivo whole mount imaging (left).
Data on the right refer to a E20 embryo.

Is your compound causing undesired cell proliferation?

The proliferative effects of low doses of a single xenobiotic or of a mixture can be measured systemically in long term exposures.

Undesired proliferative events caused by pharmacological treatments may be identified systemically in short term studies.

The figure shows that seven days after treatment with a mitogen, a thirty fold increase in luciferase activity is observed in the area where the compound was applied.

Are cells repopulating damaged tissue?

Thanks to our proprietary technology, proliferating repTOP™ mitoIRE cells produce luciferase, and can be visualized in vivo with the appropriate techniques. These cells will then show, both in the original transgenic mouse strain, and when transplanted in other animal models, their regenerative potential in the presence of tissue damage.

For instance, by inducing experimental myocardial ischemia in the repTOP™ mitoIRE mouse, it is possible to study the effects of protective or regeration-inducing agents. Stem cells derived from the repTOP™ mitoIRE mouse can be used for studying adoptive cell therapy after transplantation of these reporter cells in other models of pathology.



repTOP™ mitoIRE In Vivo Giude on Charles River web site 
repTOP™ mitoIRE technical sheet on Charles River web site




Skin Toxicity Study