Targeted deletion of a cyclic nucleotide-gated channel subunit (OCNC1): Biochemical and morphological consequences in adult mice

The olfactory cyclic nucleotide-gated channel subunit 1 (OCNC1) is required for signal transduction in olfactory receptor cells. To further investigat e the role of this channel in the olfactory system, the biochemical and mor phological consequences of targeted disruption of OCNC1 were investigated i n adult mice. Null as compared to wild-type mice had smaller olfactory bulb s, 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 olfac tory bulb in the null mice. The olfactory epithelium of the knock-out mouse was thinner and showed lower expression of olfactory marker protein and gr owth-associated protein 43, indicating decreases in both generation and mat uration of receptor cells. Tyrosine hydroxylase (TH) expression in the olfa ctory bulb, examined as a reflection of afferent activity, was reduced in t he majority of periglomerular neurons but retained in atypical or "necklace " glomeruli localized to posterior aspects of the olfactory bulb. Double la bel studies demonstrated that the remaining TH-immunostained neurons receiv ed their innervation from a subset of receptor cells previously shown to ex press a phosphodiesterase that differs from that found in most receptor cel ls. These data indicate that expression of OCNC1 is required for normal dev elopment of the olfactory epithelium and olfactory bulb. The robust express ion of TH in some periglomerular cells in the OCNC1-null mice suggests that receptor cells innervating these glomeruli may use an alternate signal tra nsduction pathway.