CILIARY NEUROTROPHIC FACTOR CONSTITUTIVELY EXPRESSED IN THE NERVOUS-SYSTEM OF TRANSGENIC MICE PROJECTS EMBRYONIC DORSAL-ROOT GANGLION NEURONS FROM APOPTOSIS

Ciliary neurotrophic factor (CNTF) is a potent survival factor for sev eral neuronal populations. It is expressed postnatally by Schwann cell s in the peripheral nervous system and by some glial and neuronal cell s in the central nervous system. We used the promoter of the neurofila ment light chain gene to produce transgenic mice that express CNTF in neurons from the beginning of neuronal differentiation. These transgen ic animals may represent a suitable model to identify neuronal cell ty pes responsive to CNTF in vivo and to study the mechanism of action of this neurotrophic factor. We show that dorsal root ganglion neurons o f transgenic mice expressing CNTF in neurons are protected from apopto sis during embryonic development: 40% of these cells undergo apoptosis between embryonic day 12.5 and postnatal day 5 in transgenic mice whe reas 60% do so in control animals. However, protection from apoptosis does not result in an increase in the total number of neurons at the e nd of development. We discuss our results with regard to CNTF potentia lities in vivo and the significance of programmed cell death during de velopment.