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The Journal of Neuroscience, November 1, 1999, 19(21):9313-9321
Targeted Deletion of a Cyclic Nucleotide-Gated Channel Subunit (OCNC1): Biochemical and Morphological Consequences in Adult Mice
Harriet Baker1, Diana. M. Cummings2, Steven D. Munger3, Joyce W. Margolis2, Linda Franzen1, Randall R. Reed3, and Frank L. Margolis2 1 Cornell University Medical College at The Burke Medical Research Institute, White Plains, New York 10605, 2 University of Maryland School of Medicine, Baltimore, Maryland 21201, and 3 The Howard Hughes Medical Institute and Department of Molecular Biology and Genetics, Johns Hopkins Medical Institutes, Baltimore, Maryland 21205
The olfactory cyclic nucleotide-gated channel subunit 1 (OCNC1) is required for signal transduction in olfactory receptor cells. To further investigate the role of this channel in the olfactory system, the biochemical and morphological consequences of targeted disruption of OCNC1 were investigated in adult mice. Null as compared to wild-type mice had smaller olfactory bulbs, suggesting compromised development of the central target of the receptor cells. Ectopic olfactory marker protein (OMP)-stained fibers localized to the external plexiform layer reflected the relative immaturity of the olfactory bulb in the null mice. The olfactory epithelium of the knock-out mouse was thinner and showed lower expression of olfactory marker protein and growth-associated protein 43, indicating decreases in both generation and maturation of receptor cells. Tyrosine hydroxylase (TH) expression in the olfactory bulb, examined as a reflection of afferent activity, was reduced in the majority of periglomerular neurons but retained in atypical or "necklace" glomeruli localized to posterior aspects of the olfactory bulb. Double label studies demonstrated that the remaining TH-immunostained neurons received their innervation from a subset of receptor cells previously shown to express a phosphodiesterase that differs from that found in most receptor cells. These data indicate that expression of OCNC1 is required for normal development of the olfactory epithelium and olfactory bulb. The robust expression of TH in some periglomerular cells in the OCNC1-null mice suggests that receptor cells innervating these glomeruli may use an alternate signal transduction pathway.
Key words: tyrosine hydroxylase; phosphodiesterase; olfactory marker protein; PAX6; atypical glomeruli; necklace glomeruli
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219313-09$05.00/0
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