Transgenic mice expressing the intracellular domain of the p75 neurotrophin receptor undergo neuronal apoptosis.
We have asked whether p75(NTR) may play a role in neuronal apoptosis by producing transgenic mice that express the p75(NTR) 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 p75(NTR) expression. Developmental loss of facial motor neurons was not observed, but induced expression of the p75(NTR) intracellular domain within adult animals led to increased motor neuron death after axotomy. Biochemical analyses suggest that these effects were not attributable to a p75(NTR)-dependent reduction in trk activation but instead indicate that the p75(NTR) intracellular domain may act as a constitutive activator of signaling cascades that regulate apoptosis in both peripheral and central neurons.
Majdan
M
M
Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada H3A 2B4.
Lachance
C
C
Gloster
A
A
Aloyz
R
R
Zeindler
C
C
Bamji
S
S
Bhakar
A
A
Belliveau
D
D
Fawcett
J
J
Miller
F D
FD
Barker
P A
PA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D005145:Face / Q000294:innervation; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D009475:Neurons, Afferent / Q000166:cytology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000166:cytology; D013564:Sympathetic Nervous System / Q000166:cytology
D015703:Antigens, CD; D016328:NF-kappa B; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases