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Science 302 (5653): 2088-2094

Copyright © 2003 by the American Association for the Advancement of Science

Negative Feedback Regulation Ensures the One Receptor-One Olfactory Neuron Rule in Mouse

Shou Serizawa,1,2* Kazunari Miyamichi,1* Hiroko Nakatani,1 Misao Suzuki,4 Michiko Saito,5 Yoshihiro Yoshihara,5 Hitoshi Sakano1,3{dagger}

Abstract: In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses only one odorant receptor (OR) gene in a monoallelic and mutually exclusive manner. Such expression forms the genetic basis for OR-instructed axonal projection of OSNs to the olfactory bulb of the brain during development. Here, we identify an upstream cis-acting DNA region that activates the OR gene cluster in mouse and allows the expression of only one OR gene within the cluster. Deletion of the coding region of the expressed OR gene or a naturally occurring frame-shift mutation allows a second OR gene to be expressed. We propose that stochastic activation of only one OR gene within the cluster and negative feedback regulation by that OR gene product are necessary to ensure the one 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.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: sakano{at}

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