Targeting Tools: Mouse-Specific p75 Immunotoxin

The long-sought mouse cholinergic toxin has been found! The mouse cholinergic immunotoxin (Cat. #IT-16) is being released for sale at the Society for Neuroscience meeting in New Orleans, November 4-9, 2000! For years ATS has received requests for a molecule that would eliminate cholinergic neurons in the basal forebrain of mice in a manner that 192-Saporin does in the rat. Because of the increasing importance of the mouse in understanding behavioral systems such as learning, memory and attention, there has been a constant interest in a molecule that could do the work. For instance, many transgenic models have given new insights into our understanding of Alzheimer’s Disease (AD), but few of them offered a clear neurodegeneration of one of the most important symptoms: cholinergic denervation. In 1995, ATS, in collaboration with Dr. Joanne Berger-Sweeney of Wellesley College, began its search for the elusive mouse p75 cholinergic toxin. The expression of p75, the low affinity neurotrophin receptor, on the surface of cholinergic basal forebrain (CBF) neurons provided an opportunity to target these neurons in the mouse, just as we had done in the rat. Conjugation of an antibody that targets p75 to saporin has produced a cytotoxin that eliminates the CBF neurons while sparing neighboring neurons that express GAD, calbindin and parvalbumin. Differences between the mouse cholinergic toxin and the rat version, and methods to use the toxin can be discussed with the experts at the ATS booth at the Society for Neuroscience meeting. We also recommend visiting the poster at the Society for Neuroscience meeting that describes the properties and activities of the new immunotoxin: A Specific Cholinergic Immunotoxin in Mice, J.E. Berger-Sweeney, S.L. Murg, M.G. Baxter, N.A. Stearns, D.A. Lappi, Abstract ID 4342, Nov 7, 2000 1:00 – 2:00 PM, Hall G-J.