Conditional ablation of mature olfactory sensory neurons mediated by diphtheria toxin receptor.
The vertebrate olfactory epithelium provides an excellent model system to study the regulatory mechanisms of neurogenesis and neuronal differentiation due to its unique ability to generate new sensory neurons throughout life. The replacement of olfactory sensory neurons is stimulated when damage occurs in the olfactory epithelium. In this study, transgenic mice, with a transgene containing human diphtheria toxin receptor under the control of the olfactory marker protein promoter (OMP-DTR), were generated in which the mature olfactory sensory neurons could be specifically ablated when exposed to diphtheria toxin. Following diphtheria toxin induced neuronal ablation, we observed increased numbers of newly generated growth associated protein 43 (GAP43)-positive immature olfactory sensory neurons. OMP-positive neurons were continuously produced from the newly generated GAP43-positive cells. The expression of the signal transduction components adenylyl cyclase type III and the G-protein alpha subunit G(alpha olf) was sensitive to diphtheria toxin exposure and their levels decreased dramatically preceding the disappearance of the OMP-positive sensory neurons. These data validate the hypothesis that OMP-DTR mice can be used as a tool to ablate the mature olfactory sensory neurons in a controlled fashion and to study the regulatory mechanisms of the neuronal replacement.
Chen
Huaiyang
H
Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616, USA. hycchen@ucdavis.edu
Kohno
Kenji
K
Gong
Qizhi
Q
D000262:Adenylyl Cyclases / Q000032:analysis / Q000235:genetics; D000818:Animals; D002923:Cilia / Q000737:chemistry / Q000502:physiology; D004167:Diphtheria Toxin / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D019922:GAP-43 Protein / Q000032:analysis / Q000235:genetics / Q000502:physiology; D044385:GTP-Binding Protein alpha Subunits / Q000032:analysis / Q000235:genetics; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051842:Olfactory Marker Protein / Q000032:analysis / Q000235:genetics / Q000502:physiology; D009831:Olfactory Mucosa / Q000294:innervation*; D018034:Olfactory Receptor Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019076:Transgenes
D004167:Diphtheria Toxin; D019922:GAP-43 Protein; D044385:GTP-Binding Protein alpha Subunits; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D051842:Olfactory Marker Protein; D011956:Receptors, Cell Surface; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3