Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth

Abstract

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 (CNTFRα). Unlike mice lacking CNTF, mice lacking CNTFRα die perinatally and display severe motor neuron deficits. Thus, CNTFRα is critical for the developing nervous system, most likely by serving as a receptor for a second, developmentally important, CNTF-like ligand.