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The Journal of Neuroscience, July 2, 2008, 28(27):6895-6903; doi:10.1523/JNEUROSCI.4579-07.2008

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Cellular/Molecular
Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

Maria Clarita Tuason,¹ Ali Rastikerdar,¹ Tanja Kuhlmann,^2,3 Cécile Goujet-Zalc,⁴ Bernard Zalc,^5,6 Samar Dib,¹ Hana Friedman,¹ and Alan Peterson¹

¹Molecular Oncology Group, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada H3A 1A1, ²Department of Neuropathology, University Medical Centre of Gottingen, D-37073 Gottingen, Germany, ³Institute of Neuropathology, University Hospital Münster, D-48149 Münster, Germany, ⁴Institute of Transgenesis and Homologue Recombination, Unité Propre de Service 44, Centre National de la Recherche Scientifique, Service d'Expérimentation Animale et de Transgénèse, 94801 Villejuif, Paris, France, ⁵Inserm, Unité 711, F-75013 Paris, France, and ⁶Faculté de Médecine, Université Pierre et Marie Curie, Institut Fédératif de Recherche 70, F-75013 Paris, France

Correspondence should be addressed to Alan Peterson, Molecular Oncology Group, Royal Victoria Hospital, McGill University, Room H5-21, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1. Email: alan.peterson{at}mcgill.ca

The gene encoding DM20 emerged in cartilaginous fish, descending from a bilaterian ancestor of the M6 proteolipid gene family. Its proteolipid protein (PLP) isoform appeared in amphibians, contains an additional 35 amino acids, and, in the mammalian CNS, is the dominant myelin protein in which it confers an essential neuroprotective function. During development, the DM20 isoform is prominent in a number of tissues, and plp/DM20 transcripts are detected in multiple progenitor populations, including those that continue to express plp/DM20 as they differentiate into myelinating oligodendrocytes. The locus also encodes isoforms with extended leader sequences that accumulate in the cell bodies of several types of neurons. Here, to locate and characterize regulatory sequences controlling the complex plp/DM20 transcription program, putative regulatory sequences, suggested by interspecies conservation, were ligated individually to a minimally promoted eGFPlacZ reporter gene. These constructs were inserted in single copy at a common site adjacent to the hypoxanthine-guanine phosphoribosyltransferase locus in embryonic stem cells and their in vivo expression programs were compared in transgenic mice. Most expressed developmental and cell-specific subprograms accommodated within the known expression phenotype of the endogenous plp/DM20 locus, thus defining multiple components of the combinatorial mechanism controlling its normal temporal and cell-specific program. Along with previously characterized nervous system enhancers, those described here should help expose the content and configuration of elements that are operational in multiple glial and neuronal lineages. The transgenic lines derived here also provide effective markers for multiple stages of glial and neuronal lineage progression.

Key words: plp/DM20; enhancers; neural crest; myelin; oligodendrocyte; Schwann cell

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Received Oct. 8, 2007; revised May 8, 2008; accepted May 19, 2008.

Correspondence should be addressed to Alan Peterson, Molecular Oncology Group, Royal Victoria Hospital, McGill University, Room H5-21, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1. Email: alan.peterson{at}mcgill.ca

This article has been cited by other articles:

				F. Guo, J. Ma, E. McCauley, P. Bannerman, and D. Pleasure Early Postnatal Proteolipid Promoter-Expressing Progenitors Produce Multilineage Cells In Vivo J. Neurosci., June 3, 2009; 29(22): 7256 - 7270. [Abstract] [Full Text] [PDF]

				G. Palais, A. Nguyen Dinh Cat, H. Friedman, N. Panek-Huet, A. Millet, F. Tronche, B. Gellen, J.-J. Mercadier, A. Peterson, and F. Jaisser Targeted transgenesis at the HPRT locus: an efficient strategy to achieve tightly controlled in vivo conditional expression with the tet system Physiol Genomics, April 10, 2009; 37(2): 140 - 146. [Abstract] [Full Text] [PDF]

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