Mice cloned from olfactory sensory neurons

Abstract

Cloning by nuclear transplantation has been successfully carried out in various mammals, including mice. Until now mice have not been cloned from post-mitotic cells such as neurons. Here, we have generated fertile mouse clones derived by transferring the nuclei of post-mitotic, olfactory sensory neurons into oocytes. These results indicate that the genome of a post-mitotic, terminally differentiated neuron can re-enter the cell cycle and be reprogrammed to a state of totipotency after nuclear transfer. Moreover, the pattern of odorant receptor gene expression and the organization of odorant receptor genes in cloned mice was indistinguishable from wild-type animals, indicating that irreversible changes to the DNA of olfactory neurons do not accompany receptor gene choice.

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Figure 1: Genetically marking post-mitotic OSNs.
Figure 2: Mice derived from OSN nuclei.
Figure 3: Mice produced from OSNs expressing the P2 odorant receptor.

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Acknowledgements

We thank L. Moring, A. Nemes, M. Mendelsohn, J. Loring, J. Dausman, A. Meissner and K. Hochedlinger for assistance during the course of these experiments; T. Cutforth, J. de Nooij, T. Jessell and J. Johnson for sharing reagents necessary for our experiments; and members of the Jaenisch, Axel and Chess laboratories for discussion and assistance during the course of these experiments, especially F. A. Ebrahimi, M. Rios, W. M. R. Rideout, L. Jackson-Grusby and B. Shykind. This research was sponsored by NIH grants to R.J. and R.A. K.B. is an Associate and R.A. is an Investigator of the Howard Hughes Medical Institute. K.E. is a Junior Fellow in the Harvard Society of Fellows.

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Correspondence to Andrew Chess or Rudolf Jaenisch.

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Supplementary information

Supplementary Figure 1

Excision of the Rosa LoxP Stop LoxP cassette in ES cells cloned from P2-IRES-GFP expressing OSNS. (JPG 35 kb)

Supplementary Figure 2

ES cells cloned from P2 expressing OSNs bear only two copies of the P2 gene. (JPG 16 kb)

Supplementary Figure 3

Genomic organization of the P2-IRES-GFP locus in cloned mice. (JPG 61 kb)

Supplementary Figure Legends (DOC 20 kb)

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Eggan, K., Baldwin, K., Tackett, M. et al. Mice cloned from olfactory sensory neurons. Nature 428, 44–49 (2004). https://doi.org/10.1038/nature02375

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