Proliferation of Schwann cells and regulation of cyclin D1 expression in an animal model of Charcot-Marie-Tooth disease type 1A.
Overexpression of PMP22 is responsible for the most common form of inherited neuropathy, Charcot-Marie-Tooth disease (CMT) type 1A. The PMP22-transgenic rat (CMT rat) is an animal model of CMT1A, and its peripheral nerves show the characteristic features of ongoing demyelination and remyelination that is also seen in CMT1A patients. Since Schwann cell proliferation is a prominent feature of peripheral nerves in inherited peripheral neuropathies, we examined proliferation and the expression of cyclin D1 in CMT rats. D-type cyclins are required for the initial steps in cell division and nuclear import is crucial for the function of cyclin D1 in promoting cell proliferation. Like normal myelinating Schwann cells in wild-type rats, remyelinating Schwann cells in CMT rats show perinuclear cyclin D1 expression. Schwann cells with nuclear cyclin D1 expression, as well as proliferating Schwann cells, were both associated with demyelinated axonal segments. Supernumerary onion bulb Schwann cells, however, do not express cyclin D1 and were not proliferating. Thus, cyclin D1 expression and its subcellular localization correlate directly with distinct physiological states of Schwann cells in this animal model of CMT1A.
Atanasoski
Suzana
S
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zurich, Switzerland.
Scherer
Steven S
SS
Nave
Klaus-Armin
KA
Suter
Ueli
U
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002451:Cell Compartmentation / Q000235:genetics; D002455:Cell Division / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D006657:Histones; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D019938:Cyclin D1