Mice cloned from olfactory sensory neurons

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.

[1]  J. Gurdon,et al.  The First Half-Century of Nuclear Transplantation , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Y. Ohta,et al.  Proliferation Markers, Proliferating Cell Nuclear Antigen, Ki67, 5-Bromo-2′-Deoxyuridine, and Cyclin D1 in Mouse Olfactory Epithelium , 2000, The Annals of otology, rhinology, and laryngology.

[3]  J. Chun,et al.  Selected comparison of immune and nervous system development. , 2001, Advances in immunology.

[4]  H Stein,et al.  Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. , 1984, Journal of immunology.

[5]  R Yanagimachi,et al.  Mice cloned from embryonic stem cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Ngai,et al.  Odorant receptor gene regulation: implications from genomic organization. , 2002, Trends in genetics : TIG.

[7]  K. Touhara,et al.  [A molecular basis for odorant recognition: olfactory receptor pharmacology]. , 2004, Nihon yakurigaku zasshi. Folia pharmacologica Japonica.

[8]  S. Tonegawa,et al.  Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[9]  W. Harris,et al.  Neurogenesis and the Cell Cycle , 2003, Neuron.

[10]  R. Axel,et al.  Genetic Ablation and Restoration of the Olfactory Topographic Map , 2000, Cell.

[11]  Susumu Tonegawa,et al.  A Complete Immunoglobulin Gene Is Created by Somatic Recombination , 2004 .

[12]  P. Mombaerts,et al.  Minigenes Impart Odorant Receptor-Specific Axon Guidance in the Olfactory Bulb , 2002, Neuron.

[13]  R. Jaenisch,et al.  Generation of mice from wild-type and targeted ES cells by nuclear cloning , 2000, Nature Genetics.

[14]  D. Schatz,et al.  Rearranging Views on Neurogenesis Neuronal Death in the Absence of DNA End-Joining Proteins , 1999, Neuron.

[15]  Randall R. Reed,et al.  Tissue and Zonal-Specific Expression of an Olfactory Receptor Transgene , 1998, The Journal of Neuroscience.

[16]  F. Alt,et al.  Late embryonic lethality and impaired V (D)J recombination in mice lacking DNA ligase IV , 1998, Nature.

[17]  T. Yagi Diversity of the cadherin‐related neuronal receptor/protocadherin family and possible DNA rearrangement in the brain , 2003, Genes to cells : devoted to molecular & cellular mechanisms.

[18]  R. Jaenisch,et al.  Nuclear transplantation: lessons from frogs and mice. , 2002, Current opinion in cell biology.

[19]  Susumu Tonegawa,et al.  A complete immunoglobulin gene is created by somatic recombination , 1978, Cell.

[20]  T. Yagi,et al.  Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  B. Goldstein,et al.  Analysis of the Globose Basal Cell Compartment in Rat Olfactory Epithelium Using GBC-1, a New Monoclonal Antibody against Globose Basal Cells , 1996, The Journal of Neuroscience.

[22]  T. Grange,et al.  Nuclear Cloning and Epigenetic Reprogramming of the Genome , 2001 .

[23]  E. Holbrook,et al.  An immunochemical, ultrastructural, and developmental characterization of the horizontal basal cells of rat olfactory epithelium , 1995, The Journal of comparative neurology.

[24]  R. Jaenisch,et al.  Monoclonal mice generated by nuclear transfer from mature B and T donor cells , 2002, Nature.

[25]  Shankar Srinivas,et al.  Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus , 2001, BMC Developmental Biology.

[26]  Mark M. Davis,et al.  Somatic recombination in a murine T-cell receptor gene , 1984, Nature.

[27]  Maurizio Zuccotti,et al.  Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei , 1998, Nature.

[28]  A. Chess,et al.  YAC transgene‐mediated olfactory receptor gene choice , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[29]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[30]  T. Yagi,et al.  Adult murine neurons: their chromatin and chromosome changes and failure to support embryonic development as revealed by nuclear transfer , 2002, Cytogenetic and Genome Research.

[31]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[32]  Kazunari Miyamichi,et al.  Negative Feedback Regulation Ensures the One Receptor-One Olfactory Neuron Rule in Mouse , 2003, Science.

[33]  Mutually exclusive expression of odorant receptor transgenes , 2000 .

[34]  R. Jaenisch,et al.  Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Richard Axel,et al.  Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium , 1993, Cell.

[36]  H. Sakano,et al.  Monoallelic expresion of the odourant receptor gene and axonal projection of olfactory sensory neurones , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[37]  Linda B. Buck,et al.  A zonal organization of odorant receptor gene expression in the olfactory epithelium , 1993, Cell.

[38]  F. Alt,et al.  A Critical Role for DNA End-Joining Proteins in Both Lymphogenesis and Neurogenesis , 1998, Cell.

[39]  R. Axel,et al.  Odorant Receptors Govern the Formation of a Precise Topographic Map , 1998, Cell.

[40]  C. Barlow,et al.  Alteration of Gene Expression by Chromosome Loss in the Postnatal Mouse Brain , 2003, The Journal of Neuroscience.

[41]  J. Rossant,et al.  Embryonic stem cells alone are able to support fetal development in the mouse. , 1990, Development.

[42]  S. Firestein,et al.  The olfactory receptor gene superfamily of the mouse , 2002, Nature Neuroscience.

[43]  S. Rehen,et al.  Chromosomal variation in neurons of the developing and adult mammalian nervous system , 2001, Proceedings of the National Academy of Sciences of the United States of America.