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In the mouse olfactory system, each olfactory sensory neuron(OSN) expresses only one odorant receptor (OR) gene in a monoallelicand mutually exclusive manner. Such expression forms the geneticbasis for OR-instructed axonal projection of OSNs to the olfactorybulb of the brain during development. Here, we identify an upstreamcis-acting DNA region that activates the OR gene cluster inmouse and allows the expression of only one OR gene within thecluster. Deletion of the coding region of the expressed OR geneor a naturally occurring frame-shift mutation allows a secondOR gene to be expressed. We propose that stochastic activationof only one OR gene within the cluster and negative feedbackregulation by that OR gene product are necessary to ensure theone receptor–one neuron rule.
1 Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan. 2 PRESTO Programs, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan. 3 CREST Programs, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan. 4 Center for Animal Resources and Development, Kumamoto University, Kumamoto 862-0976, Japan. 5 Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: sakano{at}mail.ecc.u-tokyo.ac.jp
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To whom correspondence should be addressed. E-mail: 
