MODIFICATIONS OF MYELIN BASIC-PROTEIN IN DM20 TRANSGENIC MICE ARE SIMILAR TO THOSE IN MYELIN BASIC-PROTEIN FROM MULTIPLE-SCLEROSIS

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.