Phenotypes associated with this allele

• Allele Symbol: B4galnt1^tm1Rlp
• Allele Name: targeted mutation 1, Richard L Proia
• Allele ID: MGI:2158349
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	B4galnt1^tm1Rlp/B4galnt1^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:2182107
cx2	B4galnt1^tm1Rlp/B4galnt1^tm1Rlp Hexb^tm1Rlp/Hexb^tm1Rlp	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:3578926
cx3	B4galnt1^tm1Rlp/B4galnt1^+ Hexb^tm1Rlp/Hexb^tm1Rlp	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:3578927
cx4	B4galnt1^tm1Rlp/B4galnt1^tm1Rlp St8sia1^tm1Rlp/St8sia1^tm1Rlp	involves: 129S6/SvEvTac	MGI:3851329
cx5	B4galnt1^tm1Rlp/B4galnt1^tm1Rlp St3gal5^tm1Rlp/St3gal5^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:6360944

Genotype
MGI:2182107

hm1

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

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

reproductive system

seminiferous tubule degeneration ( J:53080 )

♂

male infertility ( J:53080 )

♂ • male infertility due to degeneration of seminiferous tubules

endocrine/exocrine glands

seminiferous tubule degeneration ( J:53080 )

♂

Genotype
MGI:3578926

cx2

• Allelic Composition: B4galnt1^tm1Rlp/B4galnt1^tm1Rlp; Hexb^tm1Rlp/Hexb^tm1Rlp
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

Hexb^tm1Rlp/Hexb^tm1Rlp B4galnt1^tm1Rlp/B4galnt1^tm1Rlp mice have a hunched posture and are disheveled compared to B4galnt1^tm1Rlp/B4galnt1^tm1Rlp mice

mortality/aging

mortality/aging ( J:53080 )

N • most mice survive past 300 days of age

behavior/neurological

ataxia ( J:53080 )

• ataxic gait beginning around 7 months

impaired coordination ( J:53080 )

• rotarod performance impaired but stable through time

nervous system

abnormal neuron morphology ( J:53080 )

• fine to coarse vacuoles in the cell bodies of neurons

• vacuoles are relatively empty with relatively little electron dense material

abnormal Purkinje cell morphology ( J:53080 )

• accumulate abnormal amounts of oligosaccharide

Purkinje cell degeneration ( J:53080 )

• extensive loss of cerebellar purkinje cells by 8.5 months of age

hematopoietic system

abnormal macrophage morphology ( J:53080 )

• vacuolated macrophage found in liver, spleen and kidney

renal/urinary system

abnormal renal tubule epithelium morphology ( J:53080 )

• vacuolated epithelial cells

reproductive system

seminiferous tubule degeneration ( J:53080 )

♂

endocrine/exocrine glands

seminiferous tubule degeneration ( J:53080 )

♂

immune system

abnormal macrophage morphology ( J:53080 )

• vacuolated macrophage found in liver, spleen and kidney

Genotype
MGI:3578927

cx3

• Allelic Composition: B4galnt1^tm1Rlp/B4galnt1⁺; Hexb^tm1Rlp/Hexb^tm1Rlp
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

behavior/neurological

impaired righting response ( J:53080 )

• impaired righting reflexes seen at 23 weeks of age

impaired coordination ( J:53080 )

• progressive impairment of rotorod performance

• becoming worse than double homozygotes by 21 weeks of age

Genotype
MGI:3851329

cx4

• Allelic Composition: B4galnt1^tm1Rlp/B4galnt1^tm1Rlp; St8sia1^tm1Rlp/St8sia1^tm1Rlp
• Genetic Background: involves: 129S6/SvEvTac

mortality/aging

premature death ( J:67955 )

• 50% of mice die by 13 weeks

• 92% of mice die by 36 weeks

• 9 of 10 mice die during the tonic phase of an audiogenic seizure due to respiratory arrest

reproductive system

abnormal spermatogenesis ( J:67955 )

♂ • sperm maturation is defective

male infertility ( J:67955 )

♂

nervous system

nervous system phenotype ( J:67955 )

N • mice exhibit no neuronal cell loss or demyelination

seizures ( J:67955 )

• some mice exhibit spontaneous and/or handling-induced seizures unlike wild-type mice

audiogenic seizures ( J:67955 )

• beginning as a brief wild-running phase and followed by a clonic-tonic seizure

tonic-clonic seizures ( J:67955 )

respiratory system

abnormal breathing pattern ( J:67955 )

• 9 of 10 mice die during the tonic phase of a seizure due to respiratory arrest

behavior/neurological

seizures ( J:67955 )

• some mice exhibit spontaneous and/or handling-induced seizures unlike wild-type mice

audiogenic seizures ( J:67955 )

• beginning as a brief wild-running phase and followed by a clonic-tonic seizure

tonic-clonic seizures ( J:67955 )

Genotype
MGI:6360944

cx5

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

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