The olfactory system as a model for the analysis of the contribution of gene expression to programmed cell death.
The process of programmed cell death is frequently attenuated by inhibitors of protein and RNA synthesis. This implies that gene expression is necessary for the active elimination of some cell types. Genes such as bcl-2 and bax have been implicated in the direct control of cell death, while cellular immediate-early genes (cIEGs), such as c-fos and c-jun have been repeatedly associated with neuronal degeneration. We are using the olfactory neuroepithelium as a model system to investigate the role that expression of such genes might play in cell death. The advantages of this system is that even in the adult, there is spontaneous degeneration of olfactory receptor neurons followed by their replacement by the division and differentiation of precursors. Furthermore, the receptor neurons can be induced to die synchronously by removal of the olfactory bulb or intranasal administration of toxic agents. We have generated fos-lacZ and jun-lacZ transgenic mice that can be used to assess expression of c-fos and c-jun following these various manipulations. In addition, a line of transgenic mice has been derived that express Bcl-2 under the control of the olfactory receptor protein promoter. These mice have high levels of Bcl-2 selectively in receptor neurons of the primary neuro-epithelium and vomeronasal organ. Since in some circumstances, Bcl-2 can protect against programmed cell death these mice are being assessed for neuronal turnover under basal conditions and following olfactory bulbectomy.
Hayward
M D
MD
Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110, USA.
Morgan
J I
JI
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology*; D017781:Genes, Immediate-Early; D051379:Mice; D009830:Olfactory Bulb / Q000502:physiology; D009833:Olfactory Pathways / Q000166:cytology / Q000502:physiology*