Phenotypes Associated with This Genotype

Genotype
MGI:6116285

• Allelic Composition: Tg(Plp1-Eif2ak3*)18Pop/Tg(Plp1-Eif2ak3*)18Pop
• Genetic Background: C57BL/6J-Tg(Plp1-Eif2ak3*)18Pop

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

tremors ( J:216298 )

• mice treated with a high dose of AP20187 daily starting at P10 exhibit severe tremoring starting around P14

• mice treated with AP20187 at P10 and then treatment stopped at P15 show loss of tremoring staring around P24 and survive

• however, mice treated with AP20187 daily starting on P28 do not show obvious tremors

cellular

abnormal translation ( J:216298 )

• protein biosynthesis in the optic nerve from 18 day old mice treated with a high dose of AP20187 is suppressed, while a lose dose of AP20187 slightly, but significantly, decreases protein biosynthesis

• however, protein biosynthesis in the sciatic nerve is not altered in AP20187 treated mice

• protein biosynthesis in the optic nerve is suppressed in mice treated daily with AP20187 at 8 weeks for up to 3 weeks

homeostasis/metabolism

abnormal translation ( J:216298 )

• protein biosynthesis in the optic nerve from 18 day old mice treated with a high dose of AP20187 is suppressed, while a lose dose of AP20187 slightly, but significantly, decreases protein biosynthesis

• however, protein biosynthesis in the sciatic nerve is not altered in AP20187 treated mice

• protein biosynthesis in the optic nerve is suppressed in mice treated daily with AP20187 at 8 weeks for up to 3 weeks

mortality/aging

premature death ( J:216298 )

• mice treated with a high dose of AP20187 daily starting at P10 die by P24

• however, mice treated with AP20187 daily starting on P28 survive for at least 2 weeks

postnatal lethality ( J:216298 )

• mice treated with AP20187 daily starting on P7 die within 5 days of start of treatment

nervous system

abnormal brain white matter morphology ( J:216298 )

• size of the CNS white matter is slightly reduced in mice treated daily with AP20187 at 8 weeks for up to 3 weeks

abnormal oligodendrocyte morphology ( J:216298 )

• about 35% of oligodendrocytes in the CNS white matter of AP20187 treated mice exhibit a foamy morphology, with cells having abundant cytoplasm filled with circular, membranous structures and an oval nucleus with condensed chromatin

• a few foamy oligodendrocytes show characteristics of apoptosis, including highly condensed chromatin mass, nuclear fragmentation, and shrunken cytoplasm

• number of oligodendrocytes is moderately, but not significantly, reduced in the CNS white matter

• however, mice treated daily with AP20187 at 8 weeks for up to 3 weeks do no exhibit foamy oligodendrocytes in the CNS white matter

abnormal axon morphology ( J:216298 )

• diameter of axons in the CNS white matter is decreased in mice treated daily with AP20187 at 8 weeks for up to 3 weeks, however no effect on thickness of myelin sheaths is seen

decreased myelin sheath thickness ( J:216298 )

• thickness of myelin sheaths is decreased in mice treated with AP20187 starting at P10

dysmyelination ( J:216298 )

• degree of myelination in the CNS white matter, including the spinal cord, cerebellum, and corpus callosum, is decreased in AP20187 treated mice, indicating hypomyelination

• reduction in the percentage of myelinated axons in the white matter in 20 day old mice that began daily AP20187 treatment starting at P10

• G-ratio of myelinated axons in the CNS white matter is increased in mice treated with AP20187 starting at P10

• however, the myelination process in the peripheral nervous system is not affected in mice treated with AP20187

• treatment with AP20187 at 8 weeks of age for up to 3 weeks results in a slight reduction in the percentage of myelinated axons in the CNS white matter

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
leukoencephalopathy with vanishing white matter		DOID:0060868	OMIM:PS603896	J:216298