Targeted Deletion of a Cyclic Nucleotide-Gated Channel Subunit (OCNC1): Biochemical and Morphological Consequences in Adult Mice

Abstract

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.

Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium

“…The presence of normal afferent activity from the MOE to most OB glomeruli, although not the necklace glomeruli, depends on an intact cAMP signaling cascade (22). To provide an initial assessment of the necessity of GC-D expression for the maintenance of afferent activity in the necklace glomeruli, we took advantage of the observation that tyrosine hydroxylase (TH) expression in OB periglomerular cells is a correlate of afferent activity (22,23).…”

“…To provide an initial assessment of the necessity of GC-D expression for the maintenance of afferent activity in the necklace glomeruli, we took advantage of the observation that tyrosine hydroxylase (TH) expression in OB periglomerular cells is a correlate of afferent activity (22,23). In Gucy2d ϩ/Ϫ mice, both ␤-galpositive and ␤-gal-negative glomeruli express TH (Fig.…”

Novel Microglomerular Structures in the Olfactory Bulb of Mice

“…The relationship of these glomerular structures to each other is unclear (Greer et al, 1982;Shinoda et al, 1993;Ring et al, 1997;Baker et al, 1999;Weruaga et al, 2001), but on the whole they display a morphological and immunocytochemical profile that is distinct from that of MOB and AOB glomeruli (Shinoda et al, 1989(Shinoda et al, , 1993. Necklace glomeruli and glomeruli in the MGC are similar in size to MOB glomeruli (Weruaga et al, 2001) and are innervated by OSNs that originate in the MOE (Juilfs et al, 1997).…”

A G protein/cAMP signal cascade is required for axonal convergence into olfactory glomeruli

“…Genetic lesions of a cyclic nucleotide-gated channel subunit CNGA2 (6)(7)(8) or a G protein subunit G␣olf (9) effectively silence the odor response but do not appear to severely affect the organization of glomeruli in neonates. On the other hand, even minor changes in the OR protein cause shifts in glomerular position (10).…”