Phenotypes Associated with This Genotype

Genotype
MGI:4459456

• Allelic Composition: Tg(PLP1*)4Rsj/0
• Genetic Background: involves: CD-1

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

mortality/aging

premature death ( J:24069 , J:171534 )

• death by 8-10 months of age (J:24069)

nervous system

environmentally induced seizures ( J:24069 )

• seizure like state when picked up or otherwise disturbed

CNS inflammation ( J:161344 )

• lymphocytic infiltration is observed in the parenchyma in areas of degenerating myelin

abnormal brain morphology ( J:171534 )

• brain volume of 8 month old mutants is only 85% of brain volume in controls

astrocytosis ( J:161344 )

• a 2 fold increase at 3 months and extensive (30 times a 3 month wild-type) in 10 month old mice

abnormal myelin sheath morphology ( J:24069 )

• areas of absent, thin, or degraded myelin in the optic nerve

abnormal myelination ( J:24069 , J:161344 )

• areas of thin myelination in the optic nerve (J:24069)

• approximately 60% of the axons are thinly myelinated in 8 month old mice (J:161344)

• nude and degenerated axons are evident in 8 month old mice (J:161344)

demyelination ( J:24069 , J:161344 , J:171534 )

• partially degraded sheaths are evident in optic nerve (J:24069)

• in optic nerve of 8 month old mice, extensive unmyelinated areas (J:24069)

• at 7 months of age, but not at 2 months of age, the amount of myelin in whole brain homogenates is significantly reduced (J:24069)

• optic nerves show denuded axons in 8 month old mice (J:161344)

• whole brains show reduced levels of myelin at 10 months of age (J:161344)

• onset of demyelination in the brain at 5 months of age that gets progressively worse over time (J:171534)

behavior/neurological

lethargy ( J:24069 )

tremors ( J:24069 , J:171534 )

• head and neck tremble when raised (J:24069)

• spastic tremor at 3 months of age (J:171534)

abnormal motor coordination/balance ( J:24069 )

• unsteadiness that progresses with age

ataxia ( J:24069 )

• mice wobble with each step at 6 months

weakness ( J:24069 )

abnormal gait ( J:171534 )

• gait abnormalities at 3 months of age

hindlimb paralysis ( J:24069 )

paraparesis ( J:24069 )

• observed at 3 months of age

environmentally induced seizures ( J:24069 )

• seizure like state when picked up or otherwise disturbed

immune system

CNS inflammation ( J:161344 )

• lymphocytic infiltration is observed in the parenchyma in areas of degenerating myelin

vision/eye

abnormal electroretinogram waveform feature ( J:171534 )

• pattern electrotetinogram (PERG) waveforms show a progressive reduction in amplitude with age, indicating dysfunction of the retinal ganglion cells and of vision

• the initial PERG amplitude decrease occurs before the onset of clinical symptoms or demyelination

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple sclerosis		DOID:2377	OMIM:612594 OMIM:612595 OMIM:612596	J:161344 , J:171534