Evidence that CNS hypomyelination does not cause death of jimpy-msd mutantmice

Mice expressing three of the proteolipid protein (Plp) mutations in the mou se (jimpy, jimpy-msd, and jimpy-4J) all have a severe deficiency of CNS mye lin and oligodendrocytes (OLs), and die sometime in their 4th postnatal wee k. The prevailing view has been that the animals' shortened life span and l ack of myelin are causally related. Here we describe the survival of jimpy- msd males for as long as postnatal day (P) 210. Although these spontaneousl y occurring longer-lived jimpy-msd males show a 2- to 8-fold increase in nu mbers of myelinated axons in many CNS regions, this does not protect them f rom a later but still premature death. Investigating the cause of premature death may reveal previously undiscovered properties of the myelin genes or the cells that express them, or perhaps additional unsuspected cellular re sponses that contribute to the disease. This study identifies small accumul ations of inflammatory cells in the brain parenchyma of jimpy-msd mice as y oung as P14 and as old as P60, suggesting that the pathology of the disease produced by at least this Pip mutation may be far more complex than has be en previously recognized. Copyright (C) 2000 S. Karger AG, Basel.