Boison D and Stoffel W:
Disruption of the compacted myelin sheath of axons of the central
nervous system in proteolipid protein-deficient mice.
Proceedings of the National Academy of Sciences of the United States of
America 1994 Nov 22;91(24):11709-13
ABSTRACT
The isoproteins proteolipid protein (PLP) and DM20, the two major
integral membrane proteins of central nervous system (CNS) myelin,
are encoded by a single gene on the X chromosome and show a
different developmental expression pattern. To investigate their
functions in myelin structure and myelination, we produced
transgenic mice carrying a targeted alteration of the X
chromosome-linked Plp gene containing a deletion within exon III,
mimicking DM20, and a neo cassette in reverse orientation within
intron III. Here we show that the antisense integration of the neo
cassette disrupts the expression of the Plp gene. The ultrastructure
of the multilayer myelin sheath of all axons in the CNS of
hemizygous male or homozygous female PLP/DM20-deficient mice is
highly disordered. The apposition of the extracytoplasmic surfaces
and thereby the intraperiod dense line is lacking. The disrupted
assembly of the myelin sheath leads to a profound reduction of
conductance velocities of CNS axons, impairments in neuromotor
coordination, and behavioral changes.
