MICE DEFICIENT IN G(OLF) ARE ANOSMIC

We have used gene targeting to examine the role of the G alpha subunit , G(olf) in olfactory signal transduction. Mice homozygous for a null mutation in G(olf) show a striking reduction in the electrophysiologic al response of primary olfactory sensory neurons to a wide variety of odors. Despite this profound diminution in response to odors, the topo graphic map of primary sensory projections to the olfactory bulb remai ns unaltered in G(olf) mutants. Greater than 75% of the G(olf) mutant mice are unable to nurse and die within 2 days after birth. Rare survi ving homozygotes mate and are fertile, but mutant females exhibit inad equate maternal behaviors. Surviving homozygous mutant mice also exhib it hyperactive behaviors. These behavioral phenotypes, taken together with the patterns of G(olf) expression, suggest that G(olf) is require d for olfactory signal transduction and may also function as an essent ial signaling molecule more centrally in the brain.