Evidence that CNS hypomyelination does not cause death of jimpy-msd mutant mice.
Mice expressing three of the proteolipid protein (Plp) mutations in the mouse (jimpy, jimpy-msd, and jimpy-4J) all have a severe deficiency of CNS myelin and oligodendrocytes (OLs), and die sometime in their 4th postnatal week. The prevailing view has been that the animals' shortened life span and lack of myelin are causally related. Here we describe the survival of jimpy-msd males for as long as postnatal day (P) 210. Although these spontaneously occurring longer-lived jimpy-msd males show a 2- to 8-fold increase in numbers of myelinated axons in many CNS regions, this does not protect them from 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 responses that contribute to the disease. This study identifies small accumulations of inflammatory cells in the brain parenchyma of jimpy-msd mice as young as P14 and as old as P60, suggesting that the pathology of the disease produced by at least this Plp mutation may be far more complex than has been previously recognized.
Billings-Gagliardi
S
S
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Susan.Gagliardi@umassmed.edu
Nunnari
J N
JN
Nadon
N L
NL
Wolf
M K
MK
D000818:Animals; D002423:Cause of Death; D002490:Central Nervous System / Q000254:growth & development / Q000473:pathology*; D002493:Central Nervous System Diseases / Q000235:genetics / Q000401:mortality / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008816:Mice, Jimpy / Q000235:genetics*; D008854:Microscopy, Electron; D009154:Mutation / Q000502:physiology; D009186:Myelin Sheath / Q000473:pathology* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D016019:Survival Analysis