Regulating Peripheral Nerve Myelination

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Molecular and Cellular

Neuroscience

Vol. 20, No. 1, May 1, 2002

ISSN: 1044-7431

EISSN: 1095-9327

Identification of the Regulatory Region of the Peripheral Myelin Protein

22 (PMP22) Gene That Directs Temporal and Spatial Expression in

Development and Regeneration of Peripheral Nerves

pp. 93-109 (doi:10.1006/mcne.2002.1116)

Marcel Maier*, Philipp Berger*, Klaus-Armin Nave, Ueli Suter*, 1

*Institute of Cell Biology, Department of Biology, Swiss Federal

Institute

of Technology, ETH-Hönggerberg, CH-8093, Zurich, Switzerland

Department of Neurogenetics, Max-Planck-Institute of Experimental

Medicine, D-37075, Göttingen, Germany

(Received November 1, 2001; received in revised form January 31, 2002;

accepted February 28, 2002; published electronically June 10, 2002)

Abstract

Minor changes in PMP22 gene dosage have profound effects on the

development and maintenance of peripheral nerves. This is evident from

the genetic disease mechanisms in Charcot-Marie-Tooth disease type 1A

(CMT1A) and hereditary neuropathy with liability to pressure palsies

(HNPP) as well as transgenic animals with altered PMP22 gene dosage.

Thus, regulation of PMP22 is a crucial aspect in understanding the

function of this protein in health and disease. In this study, we have

generated

transgenic mice containing 10 kb of the 5'-flanking region of the PMP22

gene, including the two previously identified alternative promoters,

fused to a lac Z reporter gene. We show that this part of the PMP22 gene

contains the necessary information to mirror the endogenous expression

pattern in peripheral nerves during development and regeneration and in

mouse models of demyelination due to genetic lesions. Transgene

expression is strongly regulated during myelination, demyelination, and

remyelination in Schwann cells, demonstrating the crucial influence of

neuron-Schwann cell interactions in the regulation of PMP22. In

addition, the region of the PMP22 gene present on this transgene confers

also neuronal expression in sensory and motor neurons. These results

provide the crucial basis for further dissection of the elements that

direct the temporal and spatial regulation of the PMP22 gene and to

elucidate the molecular basis of the master program regulating

peripheral nerve myelination. © 2002

Elsevier Science (USA).

© Harcourt, Inc.

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