1 1 Symposium Chemosensory Receptors Satellite DEVELOPMENT ...

325 Poster Chemosensory Molecular Genetics andVNO/PheromoneBACKGROUND STRAIN DEPENDENCE OF MHC-RELATEDODORANTSKwak J. 1 , Willse A. 2 , Preti G. 1 , Curran M. 1 , Wahl J.H. 2 , Yang P. 1 ,Yamazaki K. 1 , Beauchamp G. 1 1 Monell Chemical Senses Center,Philadelphia, PA; 2 Pacific Northwest National Laboratory, Richland,WAGenes of the major histocompatibility complex (MHC) influence theurinary odors of mice. Mice can discriminate between urinary odors ofmice differing only at the MHC. Notably, mice trained to discriminatebetween MHC types for a particular mouse strain can generalize thediscrimination to other strains, suggesting that some odorants have anMHC association that is independent of background strain. Tocharacterize the effects of MHC and background genotypes on specificodorants, we analyzed the urines of congenic B6 and Balb strains thatare MHC homozygous with haplotypes H-2b or H-2k by SPME-GC/MS. A number of compounds have an MHC association that isindependent of background strain; some of these compounds mightcontribute to the generalized discrimination. However, a surprisinglylarge number of compounds (109 out of 277) have an MHC associationthat is moderated by the background genotype (i.e., there is a MHC ×background interaction). The strong background effects suggest acomplex, yet unknown, mechanism of MHC-related odor expression.This work is sponsored by DARPA under ARO Contract No. DAAD19-03-1-0109. Opinions, interpretations, conclusions, andrecommendations are those of the authors and are not necessarilyendorsed by the United States Government.326 Poster Chemosensory Molecular Genetics andVNO/PheromoneDETECTION OF THE SAME SOCIAL CUES BY THE MAINAND ACCESSORY OLFACTORY SYSTEMS: DIRECTCOMPARISON OF THEIR FUNCTIONSSpehr M. 1 , Kelliher K.R. 1 , Li X. 1 , Boehm T. 2 , Leinders-Zufall T. 1 , ZufallF. 1 1 Department of Anatomy and Neurobiology, University of MarylandSchool of Medicine, Baltimore, MD; 2 MPI Immunobiology, Freiburg,GermanyRecent work from several laboratories has shown that the traditionalview that common odors are perceived by the main olfactory systemand pheromones by the vomeronasal system needs to be revised. Wehave found that the mouse main and accessory olfactory systems detect,in part, overlapping sets of molecular cues that regulate social behaviors(e.g. urinary pheromones, MHC peptide ligands). This finding enablesus to directly compare the functional properties of both systems. Severalsurprising results are emerging. (1) Both systems can detect and processsocial chemosignals of volatile and nonvolatile nature. (2) Both systemsare highly sensitive with detection thresholds in the subnanomolarrange. (3) Coding strategies and tuning properties of individual sensoryneurons in MOE and VNO differ significantly, suggesting that differentreceptors are employed in both systems for the detection of the sameligands. (4) System-specific signal transduction pathways are used forthe detection of these cues, indicating that diverse olfactory mechanismshave evolved to assess the structural diversity of social chemosignals.(5) In behavioral tests using mice with genetic and surgical lesions,stimulation of each system by the same social cues can lead to distinctbehavioral outcomes. Therefore, the same chemosignals might mediatedifferent sexual and social behaviors through differential activation ofeach system. Support: Deutsche Forschungsgemeinschaft (DFG) andNIH/NIDCD.327 Poster Chemosensory Molecular Genetics andVNO/PheromoneA ROLE FOR MAJOR HISTOCOMPATIBILITY MOLECULESIN THE MAIN OLFACTORY BULBSalcedo E. 1 , Restrepo D. 1 1 Cellular and Developmental Biology,University of Colorado Health Sciences Center, Aurora, COThe mechanisms involved in establishing and maintaining theexquisite organization of synaptic connections found at the glomerularlayer of the main olfactory bulb (MOB) remain to be resolved. Recentfindings have linked major histocompatibility class I (MHCI) moleculesand the MHCI signaling pathway to neuronal restructuring andrefinement (Corriveau et al., 1998). In this study, we have identified aputative role for MHCI molecules in the MOB. We demonstratehistochemically that MHCI molecules are expressed in the MOB incontrol animals. Additionally, we show that mice deficient in theexpression of MHCI molecules display defects in the targeting ofolfactory sensory neurons to the MOB. Tap1 gene targeted mice lack acritical component for the expression of MHCI molecules on cellsurfaces. In these mice, we find an increased number of P2 labeledglomeruli per bulb as compared to the control littermates. Additionally,the location of these glomeruli is shifted along the rostral-caudal axis ofthe bulb as compared to the control mice. Although severely deficient inthe expression of MHCI molecules, Tap1 mice do express MHCImolecules. Therefore, we are currently characterizing mice which alsolack another component involved in presenting MHCI molecules on cellsurfaces: beta-2 microglobulin.328 Poster Chemosensory Molecular Genetics andVNO/PheromoneGENE PROFILING OF AGING IN THE MURINE OLFACTORYSYSTEM: IMMUNE SIGNATURESGetchell M.L. 1 , Vaishnav R.A. 2 , Liu H. 3 , Stromberg A.J. 3 , GetchellT.V. 2 1 Anatomy & Neurobiology, University of Kentucky, Lexington,KY; 2 Physiology, University of Kentucky, Lexington, KY; 3 Statistics,University of Kentucky, Lexington, KYGene expression levels in the olfactory epithelium (OE) and bulb(OB) of young and old mice were evaluated to identify characteristicsignatures of aging in expression profiles. Total RNA was isolated fromOEs and OBs of 3 young (1.5 months) and 3 old (20 months) C57BL/6male mice. cDNA from each tissue of each mouse was hybridized on anAffymetrix MG U74Av2 GeneChip (12 chips total). After datascrubbing and ANOVA, known genes with significant differences inexpression levels (p < 0.05) between old vs. young mice were furthercharacterized by EASE analysis to identify functional categories basedon the Gene Ontology database. For genes up-regulated in the OE,13/33 categories with significant EASE scores (< 0.05) indicatedimmune system involvement; for down-regulated genes, 0/44 immunesystem-related categories had significant EASE scores. For genes upregulatedin the OB, 10/21 categories with significant EASE scoreswere related to immune activity; for down-regulated genes, 2/17categories with significant EASE scores were immune-related. Upregulatedimmune system genes in both OE and OB werepredominantly related to autoimmunity and MHC antigen presentation.Down-regulated genes in the OB were associated with chemokines andT cell regulation. These results identify immune system activity as acharacteristic signature of aging in the murine OE and OB. Grantsupport: NIH R01 AG-16824 (TVG); NIH 1P20-RR-16481-01 (AJS).82