Phenotypes associated with this allele

• Allele Symbol: St3gal5^tm1Rlp
• Allele Name: targeted mutation 1, Richard L Proia
• Allele ID: MGI:2655771
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	St3gal5^tm1Rlp/St3gal5^tm1Rlp	involves: 129S/SvEv * C57BL/6	MGI:2655772
hm2	St3gal5^tm1Rlp/St3gal5^tm1Rlp	involves: C57BL/6JJmsSlc	MGI:6360937
cx3	B4galnt1^tm1Rlp/B4galnt1^tm1Rlp St3gal5^tm1Rlp/St3gal5^tm1Rlp	involves: 129S6/SvEvTac * C57BL/6	MGI:6360944

Genotype
MGI:2655772

hm1

• Allelic Composition: St3gal5^tm1Rlp/St3gal5^tm1Rlp
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

homeostasis/metabolism

abnormal glucose homeostasis ( J:82723 )

• homozygotes show enhanced phosphorylation of the skeletal muscle insulin receptor after ligand binding and display heightened responses in glucose and insulin tolerance tests

hypoglycemia ( J:82723 )

• under fasting conditions, 6-8 weeks old male homozygotes become hypoglycemic more rapidly than wild-type or heterozygous males

• however, no significant differences are observed in fed blood glucose levels among the three genotypes

improved glucose tolerance ( J:82723 )

• fasted 6-8 weeks old male homozygotes show a more rapid reduction of blood glucose levels than wild-type or heterozygous males at 15, 30, and 60 min after i.p. injection of a glucose solution (2 g per kg of body weight)

• after a 45% high-fat regimen for 10 weeks, male homozygotes are significantly more efficient in reducing their blood glucose to nearly baseline levels, whereas similarly treated wild-type males become glucose intolerant

increased insulin sensitivity ( J:82723 )

• fasted 6-8 weeks old male homozygotes become significantly more hypoglycemic at 15 min after an i.p. insulin injection (0.75 units per kg of body weight) than wild-type or heterozygous males, with no significant differences noted at 30 and 60 min after treatment

• after a 45% high-fat regimen for 10 weeks, male homozygotes exhibit lower insulin levels and are significantly more responsive in a glucose tolerance test than wild-type males, indicating protection from high-fat diet-induced insulin resistance

• euglycemic-hyperinsulinemic clamp studies indicate increased insulin sensitivity both in skeletal muscle and liver

abnormal lipid homeostasis ( J:82723 )

• homozygotes fail to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid

• major gangliosides present in the brain of mutant mice lack the inner a2,3-linked sialic acid contributed by GM3 synthase

• major brain gangliosides present in wild-type mice (GM1a, GD1a, GD1b, and GT1b) are not found in mutant mice

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:82723 )

N • homozygotes exhibit normal pancreatic islet morphology relative to wild-type littermates

Genotype
MGI:6360937

hm2

• Allelic Composition: St3gal5^tm1Rlp/St3gal5^tm1Rlp
• Genetic Background: involves: C57BL/6JJmsSlc

behavior/neurological

abnormal cognition ( J:171961 )

♂ • juvenile males exhibit less spontaneous alternation in the Y-maze test

decreased anxiety-related response ( J:171961 )

♂ • juvenile males spent more time in the open arms of the elevated plus maze test, indicating reduced anxiety

abnormal impulsive behavior control ( J:171961 )

♂ • juvenile males show increased impulsive behaviors in the elevated plus maze test

hyperactivity ( J:171961 )

• juvenile males and females exhibit hyperactivity in the motor activity test, Y-maze test, and elevated plus maze test

• treatment with methylphenidate hydrochloride does not ameliorate hyperactivity

Genotype
MGI:6360944

cx3

• 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