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 lines deficient in proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) were generated and characterized genetically, biochemically, and morphologically including their behavioral capacities. The plp-/-mag-/- mutant develops a rapidly progressing axon degeneration in CNS with severe cognitive and motor coordinative deficits but has a normal longevity. CNS axons of the plp-/-mbp-/-mag-/- mouse are hypomyelinated and ensheathed by "pseudomyelin" with disturbed protein and complex lipid composition. The shiverer trait in the plp-/-mbp-/-mag-/- similar to the plp-/-mbp-/- mutant is significantly ameliorated, and its lifespan is considerably prolonged. The longevity of these dysmyelinosis mouse mutants recommends them as suitable models for the long-term evaluation of stem cell therapeutic strategies.
Uschkureit
T
T
Laboratory for Molecular Neuroscience, University of Cologne, D-50931 Cologne, Germany, and Institute of Anatomy, University of Bonn, D-53115 Bonn, Germany.
Sporkel
O
O
Stracke
J
J
Bussow
H
H
Stoffel
W
W
D000818:Animals; D001369:Axons / Q000473:pathology*; D001522:Behavior, Animal; D002490:Central Nervous System / Q000378:metabolism / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D005838:Genotype; D008563:Membrane Lipids / Q000096:biosynthesis; D051379:Mice; D008818:Mice, Neurologic Mutants; D004676:Myelin Basic Protein / Q000172:deficiency* / Q000235:genetics; D018991:Myelin Proteolipid Protein / Q000172:deficiency* / Q000235:genetics; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018992:Myelin-Associated Glycoprotein / Q000172:deficiency* / Q000235:genetics; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D014158:Transcription, Genetic
D008563:Membrane Lipids; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein