Malfunctioning Gene Associated with Lou Gehrig's Disease Leads to Nerve-Cell Death in Mice (2 of 2) (IMAGE)
Caption
The JCI paper on on transgenic mouse models of TDP-43 proteinopathy recapitulates aspects of the brain and spinal cord pathology seen in FTLD-TDP and PLS. The next steps in this research are to use these mouse models to understand mechanisms of TDP-43 mediated neurodegeneration, which is essential for the design of drug discovery strategies to find disease modifying therapies for ALS, FTLD-TDP, PLS and related TDP-43 protienopathies. To that end, this "heat map" shows that the tTA/TDP-ΔNLS mice (see 5 columns on the left identified with blue bars) show dramatic down-regulation (indicated by blue regions of the heat map) and up-regulation (indicated by red regions of the heat map) of hundreds of genes compared to the non-transgenic (nTg) mice as shown in the four columns on the far right identified with green bars. These dramatic "night vs. day" like changes in gene expression in normal vs diseased TDP-43 transgenic mice scould provide important clues on mechanisms of TDP-43 mediated neurodgenerataion. Hence, these sets of genes could become targets of drug discovery for ALS, FTLD-TDP, PLS and related TDP-43 proteineinopathies.
Credit
Virginia Lee, Ph.D., University of Pennsylvania School of Medicine
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