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Volume 17, Number 18, Issue of September 15, 1997 pp. 6988-6998
Copyright ©1997 Society for NeuroscienceTransgenic Mice Expressing the Intracellular Domain of the p75 Neurotrophin Receptor Undergo Neuronal Apoptosis
Received March 4, 1997; revised June 6, 1997; accepted July 1, 1997.
Marta Majdan1, 2, Christian Lachance1, Andrew Gloster1, 2, Raquel Aloyz1, 2, Christine Zeindler1, Shernaz Bamji1, 2, Asha Bhakar1, Daniel Belliveau1, 2, James Fawcett1, Freda D. Miller1, 2, and Philip A. Barker1 1 Center for Neuronal Survival and 2 Developmental Neurobiology Laboratory, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada H3A 2B4
We have asked whether p75NTR may play a role in neuronal apoptosis by producing transgenic mice that express the p75NTR intracellular domain within peripheral and central neurons. These animals showed profound reductions in numbers of sympathetic and peripheral sensory neurons as well as cell loss in the neocortex, where there is normally little or no p75NTR expression. Developmental loss of facial motor neurons was not observed, but induced expression of the p75NTR intracellular domain within adult animals led to increased motor neuron death after axotomy. Biochemical analyses suggest that these effects were not attributable to a p75NTR-dependent reduction in trk activation but instead indicate that the p75NTR intracellular domain may act as a constitutive activator of signaling cascades that regulate apoptosis in both peripheral and central neurons.
Key words: nerve growth factor; sympathetic neuron; tumor necrosis factor; cell death; NF-kB; jun kinase
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