Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth.
Ciliary neurotrophic factor (CNTF) supports motor neuron survival in vitro and in mouse models of motor neuron degeneration and was considered a candidate for the muscle-derived neurotrophic activity that regulates motor neuron survival during development. However, CNTF expression is very low in the embryo, and CNTF gene mutations in mice or human do not result in notable abnormalities of the developing nervous system. We have generated and directly compared mice containing null mutations in the genes encoding CNTF or its receptor (CNTFR alpha). Unlike mice lacking CNTF, mice lacking CNTFR alpha die perinatally and display severe motor neuron deficits. Thus, CNTFR alpha is critical for the developing nervous system, most likely by serving as a receptor for a second, developmentally important, CNTF-like ligand.
DeChiara
Thomas M
TM
Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
Vejsada
Richard
R
Poueymirou
William T
WT
Acheson
Ann
A
Suri
Chitra
C
Conover
Joanne C
JC
Friedman
Beth
B
McClain
Joyce
J
Pan
Li
L
Stahl
Neil
N
Ip
Nancy Y
NY
Yancopoulos
George D
GD
D000818:Animals; D001933:Brain Stem / Q000002:abnormalities; D002452:Cell Count; D002470:Cell Survival; D002490:Central Nervous System / Q000002:abnormalities*; D020934:Ciliary Neurotrophic Factor; D004525:Efferent Pathways / Q000002:abnormalities / Q000254:growth & development; D005804:Genes, Lethal; D008024:Ligands; D051379:Mice; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000473:pathology*; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D013116:Spinal Cord / Q000002:abnormalities
D020934:Ciliary Neurotrophic Factor; D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor