Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons


Of the 1,000 odorant receptor (OR) genes in the mouse genome, an olfactory sensory neuron (OSN) is thought to express one gene, from one allele. This is reminiscent of immunoglobulin and T-cell receptor genes, which undergo DNA rearrangements in lymphocytes. Here, we test the hypothesis that OR gene choice is controlled by DNA rearrangements in OSNs. Using permanent genetic marking, we show that the choice by an OSN to express an allele of the OR gene M71 is irreversible. Using M71-expressing OSNs as donors for nuclear transfer, we generate blastocysts, embryonic stem (ntES) cell lines and clonal mice. DNA analysis of these cell lines, whose genome is clonally derived from an M71-expressing OSN, does not reveal DNA rearrangements or sequence alterations at the M71 locus. OSNs that differentiate from ntES cells after injection into blastocysts are not restricted to expression of M71 but can express other OR genes. Thus, M71 gene choice is irreversible but is reset upon nuclear transfer, and is not accompanied by genomic alterations.

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Figure 1: Nuclear transfer with olfactory sensory neurons.
Figure 2: Chimaeras produced with OCZ1 ntES cells generated from permanently marked, OMP-expressing OSNs.
Figure 3: Expression of the M71 OR gene is strictly monoallelic and does not switch to other OR genes.
Figure 4: ntES cell lines generated by nuclear transfer from permanently marked, M71-expressing OSNs.
Figure 5: Genomic and phenotypic analysis of M71CZ ntES cell lines.


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We thank K. Amuluru, J. Rosenberg and J. Wu for technical assistance in preparing dissociated cells, T. Bozza for helping to construct M71–IRES–tauRFP2 mice, D. Wen for collaborating to set up the tetraploid blastocyst injection technique, H. Sakano for the MOR28 probe, and R. Gao and K. Latham for advice about nuclear transfer. T.I. was supported by a postdoctoral fellowship from the Human Frontier Science Program organization. P.M. is grateful for grant support from the NIH/NIDCD.

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Correspondence to Peter Mombaerts.

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Li, J., Ishii, T., Feinstein, P. et al. Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons. Nature 428, 393–399 (2004). https://doi.org/10.1038/nature02433

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