Rumpshaker behaves like juvenile-lethal Plp mutations when combined with shiverer in double mutant mice

The phenotypes of double mutant mice whose genomes are homozygous for an Mb p (myelin basic protein) mutation and hemizygous for a juvenile-lethal Plp (proteolipid protein) mutation were compared in earlier studies. The result s suggested that the shiverer Mpb mutation might have some unexplained abil ity to partially rescue oligodendrocytes (OLs) from the 'death sentence' th at is imposed by the Plp mutations. Conversely, they also indicated that th e juvenile-lethal Plp mutations may normalize shiverer OL morphology by red ucing the numbers of microprocesses. The Plp mutation rumpshaker produces a mild hypomyelination without reduction in OL numbers and a normal lifespan . This report describes double mutant mice combining two Mbp mutations with rumpshaker, utilizing a common B6C3F1 hybrid-based genetic background. ini tial studies on B6C3F1 rumpshaker optic nerve and spinal cord white matter showed unanticipated signs of OL death, with morphologic criteria suggestiv e of an apoptotic mechanism. In shiverer*rumpshaker double mutant mice, thi s small class of dying cells could not be identified. White matter morpholo gy was similar to that of mice expressing only the shiverer mutation, excep t that OL microprocesses were far less abundant. This evidence suggests tha t, despite their distinctive phenotypic differences, rumpshaker may share m ore characteristics with the juvenile-lethal Plp mutations than has previou sly been recognized. Copyright (C) 2001 S. Karger AG, Basel.