Phenotypes Associated with This Genotype

Genotype
MGI:5697875

• Allelic Composition: Tg(Plp1-LMNB1)1108Qsp/0
• Genetic Background: involves: FVB/N

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

mortality/aging

premature death ( J:226169 )

• mice do not survive beyond 15 months

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:226169 )

• mice exhibit severe age-dependent motor dysfunction and forelimb atrophy

ataxia ( J:226169 )

forelimb paralysis ( J:226169 )

• mice exhibit age-dependent forelimb paralysis

hematopoietic system

microgliosis ( J:226169 )

• microgliosis that is localized to the lateral and ventral white matter regions of the spinal cord

homeostasis/metabolism

abnormal lipid level ( J:226169 )

• mice show an age-dependent reduction in myelin-enriched lipid species

decreased cholesterol level ( J:226169 )

• reduction in total cholesterol in spinal cord tissue at 3 and 13 months of age

abnormal phospholipid level ( J:226169 )

• total phospholipid levels are reduced in spinal cord tissue at 13 months, but not 3 months, of age, with a significant reduction of phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, and sphingomyelin

• subtle reductions in amounts of phosphatidylethanolamine and phosophatidylcholine species in 3 month spinal cords

abnormal sphingomyelin level ( J:226169 )

• reduction in sphingomyelin levels in the spinal cord tissue at 13 months of age

immune system

microgliosis ( J:226169 )

• microgliosis that is localized to the lateral and ventral white matter regions of the spinal cord

nervous system

microgliosis ( J:226169 )

• microgliosis that is localized to the lateral and ventral white matter regions of the spinal cord

astrocytosis ( J:226169 )

• astrogliosis in the spinal cord

• increase in GFAP staining in 13 month old mice, with a redistribution of reactive astrocytes toward the gray matter

abnormal oligodendrocyte morphology ( J:226169 )

• age-dependent chromatin alterations in oligodendrocytes

increased oligodendrocyte number ( J:226169 )

• oligodendrocyte number at 8 and 13 months of age is increased in the spinal cord

decreased spinal cord ventral horn cell number ( J:226169 )

• loss of neuronal cell bodies in the ventral horn of 13 month old cervical spinal cord

abnormal spinal cord white matter morphology ( J:226169 )

• spinal cord exhibits severe vacuolar degeneration in the white matter of the ventral and lateral regions of the cord and is most severe are later time points

• spinal cord degeneration is most pronounced in the cervical region

• however, the cerebellum and corpus callosum do not show any pathological changes, and brainstem shows minimal involvement

axon degeneration ( J:226169 )

• 13 month old spinal cords show axonal degeneration

demyelination ( J:226169 )

• age-dependent demyelination in spinal cords

• 13 month old spinal cord shows loss of general organization of myelinated axons with widespread myelin and axonal degeneration, high levels or astrogliosis, very thin myelin suggestive of remyelination, redundant myelin, and unmyelinated axons

• large vacuoles are often seen with and without an axon

skeleton

kyphosis ( J:226169 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adult-onset autosomal dominant demyelinating leukodystrophy		DOID:0060785	OMIM:169500	J:226169