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Published Online October 30, 2003
Science DOI: 10.1126/science.1089122

Research Articles

Submitted on July 14, 2003
Accepted on October 17, 2003

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

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

1 Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan; PRESTO, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.
2 Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan.
3 Center for Animal Resources and Development, Kumamoto University, Kumamoto 862-0976, Japan.
4 Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
5 Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan; CREST, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.

* To whom correspondence should be addressed. E-mail: sakano{at}mail.ecc.u-tokyo.ac.jp.

In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses only one odorant receptor (OR) gene in a mono-allelic and mutually exclusive manner. Such expression forms the genetic basis for OR-instructed axonal projection of OSNs to the olfactory bulb (OB) 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 frame-shift mutation in that gene 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.


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