Press Releases
Dec. 6, 2007

Deletion of the core-H region in mice abolishes the expression of three proximal odorant receptor genes in cis

  • Hirofumi Nishizumi (Department of Biophysics and Biochemistry)
  • Kouhei Kumasaka (Department of Biophysics and Biochemistry)
  • Nobuko Inoue (Department of Biophysics and Biochemistry)
  • Ai Nakashima (Department of Biophysics and Biochemistry)
  • Hitoshi Sakano (Department of Biophysics and Biochemistry)
Figure 1

Figure1: A model for the maintenance of the one neuron- one receptor rule. We assume that an activation complex formed at the LCR interacts with one promoter site (P) in the cluster, thus activating only one member of the OR genes. When this gene is functional, the OR gene products, most likely OR proteins, inhibit further activation of other OR gene clusters, possibly by methylating (-CH3) the LCR sequences and/or phosphorylating ( P ) nuclear factors binding to the LCR. Filled boxes represent OR genes.

We have previously reported a 2.1kb homology (H) sequence, conserved between mouse and human, regulates the odorant receptor (OR) gene MOR28 in transgenic mice. Here, we narrowed down the essential sequences of the H to a core of 124bp, using a transient expression system in zebrafish embryos. Transgenic experiments in mice demonstrated that the core-H sequence is sufficient to endow expression of the MOR28 minigene. Deletion and mutation analyses of the core-H region revealed two homeodomain sequences to be essential for the H enhancer activity. Targeted deletion of the core-H abolished expression of three proximal OR genes, MOR28, MOR10, and MOR83, in cis, indicating the presence of another LCR/enhancer in the downstream region, that regulates four distal OR genes in the same MOR28 cluster. In the heterozygous mice, the H - phenotype of the mutant allele was not rescued by the wild-type H + allele in trans.

Published in Proc. Natl. Acad. Sci. USA 104, 20067-20072, 2007