Early onset of axonal degeneration in double (plp-/-mag-/-) and hypomyelinosis in triple (plp-/-mbp-/-mag-/-) mutant mice

Double (plp-/-mag-/-) and triple (plp-/-mbp-/-mag-/-) null-allelic mouse li nes deficient in proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) were generated and characterized gene tically, biochemically, and morphologically including their behavioral capa cities. The plp-/-mag-/- mutant develops a rapidly progressing axon degener ation in CNS with severe cognitive and motor coordinative deficits but has a normal longevity. CNS axons of the plp-/-mbp-/-mag-/- mouse are hypomyeli nated and ensheathed by "pseudomyelin" with disturbed protein and complex l ipid composition. The shiverer trait in the plp-/-mbp-/-mag-/- similar to t he plp-/-mbp-/- mutant is significantly ameliorated, and its lifespan is co nsiderably prolonged. The longevity of these dysmyelinosis mouse mutants re commends them as suitable models for the long-term evaluation of stem cell therapeutic strategies.