Phenotypes Associated with This Genotype

Genotype
MGI:4999603

• Allelic Composition: Fa2h^tm1.1Hama/Fa2h^tm1.1Hama
• Genetic Background: involves: 129 * C57BL/6

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

nervous system

nervous system phenotype ( J:171655 )

N • nerve conduction velocities and compound muscle action potentials are similar to controls

abnormal cerebellum morphology ( J:171655 )

• decrease in myelin lipid levels in the cerebellum compared to controls at 12 months of age but not at 3 months of age

abnormal Purkinje cell morphology ( J:171655 )

• while the overall number of Purkinje cells is similar to controls, regions with smaller sized or absent Purkinje neurons relative to controls are seen

decreased Purkinje cell size ( J:171655 )

abnormal astrocyte morphology ( J:171655 )

• hypertrophic astrocytes are noted in the optic nerve

abnormal axon morphology ( J:171655 )

• axons in the optic nerve and spinal cord have abnormally dense cytoplasm, abnormal accumulations of organelles, and myelin sheaths are detected that do not surround an identifiable axon

• regions of profound axon loss are seen in several optic nerves

• grossly enlarged axons usually containing whorls of disorganized neurofilaments as well as dense bodies, lysosomes, and mitochondria are seen

abnormal myelin sheath morphology ( J:171655 )

• some enlarged axons are surrounded by an attenuated myelin sheath

• only occasional axons with attenuated myelin sheaths are detected in the sciatic nerve

abnormal optic nerve morphology ( J:171655 )

• axon loss and demyelination are seen in the optic nerve

• in regions where myelinated axons are largely absent mononuclear cells (likely macrophages or microglia) are present

• hypertrophic astrocytes are noted in the optic nerve

demyelination ( J:171655 )

• of some optic nerve axons

homeostasis/metabolism

abnormal lipid level ( J:171655 )

• decrease in myelin lipid levels in the cerebellum compared to controls at 12 months of age but not at 3 months of age

decreased cholesterol level ( J:171655 )

• in the spinal cord at 14 months of age

abnormal galactolipid level ( J:171655 )

• hFA-GalCer galactolipids are absent from the brain, spinal cord, and sciatic nerve

• total galactolipid levels are lower compared to heterozygous controls

• total loss of brain hFA-galactolipids at 3 months of age

behavior/neurological

abnormal learning/memory/conditioning ( J:171655 )

• impairment in reversal learning in a water T maze at 3 months of age

abnormal motor learning ( J:171655 )

• impaired motor learning at 12 months of age

• impairment is first detected at 7 months of age

abnormal spatial learning ( J:171655 )

• impairment in initial and reversal learning in a morris water maze at 4 months of age

impaired coordination ( J:171655 )

• at 12 months of age on a rotarod at all speeds greater than 4 rpm

• impairment is first detected at 7 months of age

decreased vertical activity ( J:171655 )

• at 12 months of age

• reduction in vertical activity is more severe than that in horizontal activity

decreased locomotor activity ( J:171655 )

• decrease in spontaneous activity at 12 months of age

vision/eye

abnormal optic nerve morphology ( J:171655 )

• axon loss and demyelination are seen in the optic nerve

• in regions where myelinated axons are largely absent mononuclear cells (likely macrophages or microglia) are present

• hypertrophic astrocytes are noted in the optic nerve

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spastic paraplegia 35		DOID:0110786	OMIM:612319	J:171655