Fg. Mastronardi et al., MODIFICATIONS OF MYELIN BASIC-PROTEIN IN DM20 TRANSGENIC MICE ARE SIMILAR TO THOSE IN MYELIN BASIC-PROTEIN FROM MULTIPLE-SCLEROSIS, The Journal of clinical investigation, 97(2), 1996, pp. 349-358
Transgenic mice containing different numbers of transgenes (2-70) of t
he myelin proteolipid protein DM20 were phenotypically normal up to 3
mo of age, after which the mice containing 70 copies of the transgene
spontaneously demyelinated and died at 10-12 mo. Since we demonstrated
that demyelination in multiple sclerosis involved specific chemical c
hanges in myelin basic protein (MBP), we investigated the MBP in our t
ransgenic line for similar changes. Both the total amount of MBP in br
ain and the MBP mRNA levels were unaffected at the different ages. All
the isoforms (14 -21 kD) of MBP were present, but the microheterogene
ity (a posttranslational event) was changed resulting in a higher prop
ortion of the less cationic components reminiscent of the changes in M
BP found in multiple sclerosis. An increased amount of the citrullinat
ed form of MBP was found by Western blot analysis. Immunogold labeling
of cryosections of brain revealed a greater density of particles with
the anticitrulline antibody at 10 mo and that the levels of peptidyla
rginine deiminase (which deiminates protein-bound arginine to citrulli
ne) were increased. This stable transgenic line represents a useful an
imal model for the human disease multiple sclerosis.