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One neuron-one receptor rule in the mouse olfactory system.
Shou Serizawa1, Kazunari Miyamichi, Hitoshi Sakano
1PRESTO program of Japan Science and Technology Agency, Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.
Trends in Genetics : TIG
|November 4, 2004
Summary
Mammalian olfactory receptor (OR) genes are expressed one per neuron. OR protein inhibits other OR gene activation, maintaining the one neuron-one receptor rule.
Area of Science:
- Neuroscience
- Genetics
- Olfactory system biology
Background:
- Mammalian olfactory receptor (OR) genes exhibit mutually exclusive and monoallelic expression in olfactory sensory neurons (OSNs).
- This phenomenon is analogous to antigen receptor gene expression in lymphocytes.
- Mechanisms for OR allelic exclusion, such as DNA rearrangement, were previously investigated.
Purpose of the Study:
- To elucidate the mechanism underlying allelic exclusion of odorant receptor genes in the mammalian olfactory system.
- To investigate the role of olfactory receptor protein in regulating gene expression.
- To understand how the one neuron-one receptor rule is maintained.
Main Methods:
- Cloning experiments using mature OSN nuclei to assess OR repertoire.
- Transgenic experiments to investigate the function of OR proteins.
- Analysis of gene expression regulation in olfactory sensory neurons.
Main Results:
- Irreversible gene translocation was excluded as a mechanism for OR allelic exclusion.
- Cloned mice from OSN nuclei expressed the full OR repertoire, ruling out irreversible translocation.
- Transgenic experiments suggested an inhibitory role for the OR protein in preventing activation of other OR genes.
Conclusions:
- Allelic exclusion in the olfactory system is likely achieved through stochastic OR gene activation.
- Negative-feedback regulation by the OR gene product plays a crucial role.
- These mechanisms ensure the maintenance of the one neuron-one receptor rule in OSNs.