Olfactory markerprotein (OMP)genedeletion causesaltered physiological activity ofolfactory sensory neurons (olfactory bulb/tyrosine hydroxylase/cholecystokinin/electroolfactogram)

Olfactory markerprotein (OMP)isan abundant, phylogenetically conserved, cytoplasmic protein of unknownfunction expressed almostexclusively inmature olfactory sensory neurons. Toaddress itsfunction, wegener- atedOMP-deficient micebygenetargeting inembryonic stem cells. Wereport thatthese OMP-null micearecompromised intheir ability torespond toodorstimuli, providing insight to OMP function. Themaximal electroolfactogram response of theolfactory neuroepithelium toseveral odorants was20-40% smaller inthemutants compared withcontrols. Inaddition, theonsetandrecovery kinetics following isoamyl acetate stimulation areprolonged inthenull mice. Furthermore, the ability ofthemutants torespond tothesecond odorpulse of apair isimpaired, overarange ofconcentrations, compared withcontrols. Theseresults imply that neural activity directed toward theolfactory bulbisalsoreduced. Thebulbar pheno- typeobserved intheOMP-null mouseisconsistent withthis hypothesis. Bulbar activity oftyrosine hydroxylase, therate limiting enzyme ofcatecholamine biosynthesis, andcontent of theneuropeptide cholecystokinin arereduced by65%and 50%,respectively. Thissimilarity topostsynaptic changes in geneexpression induced byperipheral olfactory deafferenta- tion ornaris blockade confirms that functional neural activity isreduced inboththeolfactory neuroepithelium andthe olfactory nerve projection tothebulbintheOMP-null mouse. These observations provide strong support fortheconclusion thatOMP isa novelmodulatory component oftheodor detection/signal transduction cascade. Odordetection occurs inolfactory cilia wheresignal trans- duction isbelieved tobeinitiated byastimulus molecule interacting withaseven-transmembrane domainG protein- coupled receptor. Subsequent activation ofG protein- mediated second messenger systems leads tocation channel opening andaction potential generation (1). Manyproteins of theodordetection/signal tranduction cascade areeither abun- dantly orselectively expressed inolfactory sensory neurons (1-4). Although these proteins arestructurally homologous to proteins involved insignal transduction inother cell types, attempts todemonstrate functional activity ofolfactory re- ceptor molecules inheterologous systems havebeenlargely unsuccessful (see, however, ref. 5). Thebasis forthis lack of success isunknownbutmayrelate tothedifficulty inchoosing anoptimal stimulus/receptor