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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
PubMed

Insights

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.

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