Phenotypes Associated with This Genotype

Genotype
MGI:6360944

• Allelic Composition: B4galnt1^tm1Rlp/B4galnt1^tm1Rlp; St3gal5^tm1Rlp/St3gal5^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

mortality/aging

premature death ( J:96830 )

• majority of ice die over the subsequent 2 months after weaning at 3 weeks, with only rare mice surviving to 5 months of age

behavior/neurological

tremors ( J:96830 )

• mice develop tremors at 2 weeks of age which become more severe with increasing age

ataxia ( J:96830 )

• mice develop ataxia at 2 weeks of age which becomes more severe with increasing age

paraparesis ( J:96830 )

• mice develop hind limb weakness at 2 weeks of age which becomes more severe with increasing age

cellular

increased brain apoptosis ( J:96830 )

• apoptotic cells in the cerebral cortex

homeostasis/metabolism

abnormal lipid homeostasis ( J:96830 )

• sialidase treatment of the acidic lipid fraction results in the conversion of the major ganglioside species to neolactotetraosylceramide or lactotetraosylceramide instead of the mono-sialyl ganglioside GM1 as in wild-type mice

abnormal ganglioside level ( J:96830 )

• absence of the major brain gangliosides species ceramide and hexosylceramide

• presence of lactosylceramide as a major acidic lipid species and the complex sulfatide SM3 (lactosylceremiade sulfate) in the brain which are not seen in wild-type mice

• interruption of ganglioside synthesis in neurons resulting in a shift toward synthesis of lactosylceramide and lactosylcermaide-3-sulfate

nervous system

increased brain apoptosis ( J:96830 )

• apoptotic cells in the cerebral cortex

decreased brain size ( J:96830 )

• brains are slightly smaller at 1 month of age and show a progressive decrease in size between 2-3 months of age

abnormal cerebellum white matter morphology ( J:96830 )

• vacuolization in the cerebellar white matter is seen at 1 month of age

abnormal brainstem morphology ( J:96830 )

• vacuolization in the brain stem fiber tracts is seen at 1 month of age

brain vacuoles ( J:96830 )

• vacuolization in the spinal and cerebellar white matter and in the brainstem fiber tracts is seen at 1 month of age

astrocytosis ( J:96830 )

• mice show an astrocytic response in the brains, especially in the surrounding white matter regions, prominent around the corpus callosum and in the white matter tract of the cerebellum and within the cerebellar molecular layer

abnormal oligodendrocyte morphology ( J:96830 )

• oligodendrocytes contain massive cytoplasmic vacuoles

• however, oligodendrocyte differentiation is normal

abnormal axon morphology ( J:96830 )

• tubulovesicular structures are seen in the cerebellar axons

• transverse bands, normally present in regularly arrayed electron densities in the periaxonal space, are not properly formed

abnormal paranode morphology ( J:96830 )

• paranode loops that face away from the axon are seen

abnormal paranodal axoglial junction morphology ( J:96830 )

• paranodal loops of myelin in the node of Ranvier that are not tightly associated with the axonal membrane, indicating abnormal axonal-glial interactions

abnormal spinal cord white matter morphology ( J:96830 )

• vacuolization in the spinal white matter is seen at 1 month of age

neurodegeneration ( J:96830 )

axon degeneration ( J:96830 )

• degeneration of myelinated axons

axonal spheroids ( J:96830 )

• axonal spheroid formation is seen in the cerebellar white matter and granular layers, indicating neurodegeneration