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Promoter analysis of the CMT1A‐disease gene PMP22 in vivo
Author(s) -
Maier M.,
Berger P.,
Nave K. A.,
Suter U.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.45_2.x
Subject(s) - peripheral myelin protein 22 , biology , remyelination , schwann cell , transgene , myelin , gene , gene knockin , gene expression , microbiology and biotechnology , genetics , gene dosage , genetically modified mouse , neuroscience , phenotype , central nervous system
The peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann Cells and in neurons of the peripheral nervous system where it accounts for 2–5% of total protein in the myelin sheat. 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 1 A (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 describe important regulatory elements of PMP22 by the generation of transgenic mice containing 10 kb of 5′‐flanking region of the PMP22 gene, including the two previously identified alternative promoters, fused to a lacZ 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, 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. These results provide the crucial basis for the ongoing 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.