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doi: 10.1242/10.1242/jcs.00121

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Conditional ablation of the Mat1 subunit of TFIIH in Schwann cells provides evidence that Mat1 is not required for general transcription

Nina Korsisaari^1,*, Derrick J. Rossi^1,*, Anders Paetau², Patrick Charnay³, Mark Henkemeyer⁴ and Tomi P. Mäkelä^1,

¹ Haartman Institute and Helsinki University Central Hospital, Biomedicum Helsinki, PO Box 63, Haartmaninkatu 8, 00014 University of Helsinki, Finland
² Department of Pathology, Haartman Institute and Helsinki University Central Hospital, P.O. Box 21, 00014 University of Helsinki, Finland
³ Unité 368 de l'Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure, 46 rue d'Ulm, F-75230 Paris Cedex 05, France
⁴ Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9133, USA

Author for correspondence (e-mail: tomi.makela{at}helsinki.fi)

Accepted 27 August 2002

The mammalian Mat1 protein has been implicated in cell cycle regulation as part of the Cdk activating kinase (CAK), and in regulation of transcription as a subunit of transcription factor TFIIH. To address the role of Mat1 in vivo, we have used a Cre/loxP system to conditionally ablate Mat1 in adult mitotic and post-mitotic lineages. We found that the mitotic cells of the germ lineage died rapidly upon disruption of Mat1 indicating an absolute requirement of Mat1 in these cells. By contrast, post-mitotic myelinating Schwann cells were able to attain a mature myelinated phenotype in the absence of Mat1. Moreover, mutant animals did not show morphological or physiological signs of Schwann cell dysfunction into early adulthood. Beyond 3 months of age, however, myelinated Schwann cells in the sciatic nerves acquired a severe hypomyelinating morphology with alterations ranging from cells undergoing degeneration to completely denuded axons. This phenotype was coupled to extensive proliferation and remyelination that our evidence suggests was undertaken by the non-myelinated Schwann cell pool. These results indicate that Mat1 is not essential for the transcriptional program underlying the myelination of peripheral axons by Schwann cells and suggest that the function of Mat1 in RNA polymerase II-mediated transcription in these cells is regulatory rather than essential.

Key words: RNA polymerase II, Krox-20, Testis, Non-myelinated, Mouse

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TFIIH kinase: for specific not general transcription

JCS 2002 115: 2205. [Full Text]  

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