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Journal of Neuroscience, Vol 15, 5502-5513, Copyright © 1995 by Society for Neuroscience
Adhesive properties of proteolipid protein are responsible for the compaction of CNS myelin sheaths
D Boison, H Bussow, D D'Urso, HW Muller and W Stoffel
Institut fur Biochemie, Medizinische Fakultat, Universitat Koln, Germany.
We have studied the molecular function of proteolipid protein (PLP), the
main integral membrane protein of CNS myelin, by generating mice lacking
PLP expression. Here, we demonstrate that these PLP-minus mice show no
pleiotropism as mice carrying point mutations within the PLP gene. The
expression of other myelin genes (myelin basic protein, MBP; myelin
associated glycoprotein, MAG; UDP-galactose-ceramide galactosyl
transferase, CGT) is unimpaired on the RNA level. Protein level
immunofluorescence analysis by confocal microscopy reveals that in PLP-
minus mice there is a complete absence of PLP, a scattered appearance of
MBP, and MAG expressed more widely in regions lacking MBP staining, which
may be a compensatory mechanism. In electron microscopy the myelin lamellae
of the ensheathed CNS axons are loosely wrapped with wide extracellular
spaces between turning loops. Intraperiod dense lines are missing. The
lateral loops of the paranode form regular axoglial junctions. In PLP-minus
mice axons form regular axoglial junctions. In PLP-minus mice axons with
large diameters are loosely myelinated, whereas small axons remain
unmyelinated. Functionally, the mutant mice show deficits in their
locomotor activity. We propose that adhesion properties of the
extracellular domains of PLP are responsible for the tight apposition of
the plasma membrane processes of oligodendrocytes wrapping axons to form
the compact myelin sheath.
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