Expression of Bcl-2 extends the survival of olfactory receptor neurons in the absence of an olfactory bulb.
In the olfactory neuroepithelium, the number of olfactory receptor neurons (ORNs) is maintained at a relatively constant level by a precise balance between the elimination of mature receptors and proliferation of their precursors. However, little is known of the mechanisms that couple alterations in receptor death rates to changes in precursor proliferation. To investigate this relationship, we generated a line of mice expressing Bcl-2, a protein with anti-apoptotic properties, in mature olfactory receptor neurons using the Olfactory Marker Protein (OMP) promoter. OMP-bcl-2 transgenic mice showed selective expression of Bcl-2 in mature sensory neurons of the olfactory neuroepithelium (ONE) and vomeronasal organ. Olfactory bulbectomy (OBX) resulted in the death of mature receptor neurons followed by the sustained proliferation of their precursors in wild-type and OMP-bcl-2 transgenic mice. The persistently enhanced proliferation of olfactory neuroblasts that followed bulbectomy was indistinguishable between transgenic and non-transgenic mice. However, receptor neurons that were subsequently born in the absence of the bulb had longer life spans in OMP-bcl-2 mice. The increased proliferation of neuroblasts and extended life spans combined to restore near normal numbers of olfactory receptors in bulbectomized OMP-bcl-2 mice. A model is proposed to explain the dissociation of death and proliferation in OMP-bcl-2 transgenic mice.
Hayward
Michael D
MD
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale St. Memphis, TN 38105-2794, United States.
Bocchiaro
Christopher M
CM
Morgan
James I
JI
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D003714:Denervation; D015870:Gene Expression; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009830:Olfactory Bulb / Q000473:pathology* / Q000601:surgery; D051842:Olfactory Marker Protein; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2