Impaired olfactory behavior in mice deficient in the α subunit of Go

The ability to respond to chemical signals is essential for the survival and reproduction of most organisms. Olfactory signaling involves odorant receptor-mediated activation of Golf, a homologue of Gs, on the dendrites of olfactory neurons. Olfactory receptor cells, however, also express G alpha i2 and G alpha o on their axons, with all neurons expressing Go and a subset Gi2. Despite their abundance, possible contributions of Go and Gi2 to chemoreception remain unexplored. We investigated whether homologous recombinant mice deficient in the alpha subunit of Go are able to respond to odorants, whether possible olfactory impairments are dependent on genetic background, and whether formation of glomeruli in their olfactory bulbs is compromised. In an olfactory habituation/dishabituation test, Go-/- mice were unresponsive when exposed to odorants. Analysis of variance shows that performance of Go+/- mice crossed into the CD-1 background is also diminished in this test compared to their Go+/+ counterparts. Following food deprivation, Go-/- mice in the 129 Sv-ter/C57BL/6 genetic background were unable to locate a buried food pellet until they were 10 weeks of age after which they performed as well as their litter mate controls. However, CD-1 Go-/- mice could locate a buried food pellet even when tested immediately after weaning. Despite their compromised olfactory responsiveness, histological examination did not reveal gross alterations in the olfactory bulbs of Go-/- mice. Thus, G alpha o is necessary for the expression of olfactory behavior under normal conditions and dependent on genetic background, but is not essential for the formation and maintenance of glomeruli.