Phenotypes associated with this allele

• Allele Symbol: Glb1^tm1Adz
• Allele Name: targeted mutation 1, Alessandra d'Azzo
• Allele ID: MGI:3579514
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Glb1^tm1Adz/Glb1^tm1Adz	involves: 129P2/OlaHsd	MGI:3581421
hm2	Glb1^tm1Adz/Glb1^tm1Adz	involves: 129/Sv * C57BL/6	MGI:3581423
cx3	Galc^twi/Galc^twi Glb1^tm1Adz/Glb1^tm1Adz	involves: 129P2/OlaHsd * C57BL/6J * CE/J	MGI:4452612
cx4	Galc^twi/Galc^twi Glb1^tm1Adz/Glb1^+	involves: 129P2/OlaHsd * C57BL/6J * CE/J	MGI:4452613

Genotype
MGI:3581421

hm1

• Allelic Composition: Glb1^tm1Adz/Glb1^tm1Adz
• Genetic Background: involves: 129P2/OlaHsd

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

nervous system

abnormal brain morphology ( J:38620 )

• accumulation of G_M1-ganglioside and GA1 in the brain, however did not see any abnormalities in content or distribution of other lipids

• amount of brain ganglioside sialic acid and G_M1-ganglioside increased rapidly and dramatically from 3 weeks to 3.5 months of age

abnormal neuron morphology ( J:38620 )

• exhibited swollen neurons containing storage materials throughout the brain as early as 3 weeks of age

• by 5 weeks, neuron storage was seen in almost all neurons in the cerebrum, cerebellum, brainstem, spinal cord, and dorsal root ganglia

behavior/neurological

tremors ( J:38620 )

• apparent in older mice

ataxia ( J:38620 )

• apparent in older mice

abnormal gait ( J:38620 )

• apparent in older mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
GM1 gangliosidosis		DOID:3322		J:38620

Genotype
MGI:3581423

hm2

• Allelic Composition: Glb1^tm1Adz/Glb1^tm1Adz
• Genetic Background: involves: 129/Sv * C57BL/6

nervous system

abnormal brainstem morphology ( J:98543 )

• increased total ganglioside content in the cerebellum and cerebrum-brainstem

• N-butyldeoxygalacto-nojirimycin (NB-DGJ), an imino sugar that inhibits ganglioside biosynthesis, significantly reduced total ganglioside and GM1 content when administered from P9-P15

abnormal cerebellum morphology ( J:98543 )

• increased total ganglioside content in the cerebellum and cerebrum-brainstem

• N-butyldeoxygalacto-nojirimycin (NB-DGJ), an imino sugar that inhibits ganglioside biosynthesis, significantly reduced total ganglioside and GM1 content when administered from P9-P15

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
GM1 gangliosidosis		DOID:3322		J:98543

Genotype
MGI:4452612

cx3

• Allelic Composition: Galc^twi/Galc^twi; Glb1^tm1Adz/Glb1^tm1Adz
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * CE/J

mortality/aging

premature death ( J:63197 )

• average lifespan is 74.3 days with some surviving up to 94 days, a significant extension of longevity compared with mice homozygous for twitcher only

hematopoietic system

enlarged spleen ( J:63197 )

• macrophage infiltration in the lymph follicles of the spleen at 94 days of age

abnormal macrophage physiology ( J:63197 )

immune system

enlarged spleen ( J:63197 )

• macrophage infiltration in the lymph follicles of the spleen at 94 days of age

abnormal macrophage physiology ( J:63197 )

liver/biliary system

abnormal liver morphology ( J:63197 )

• at 94 days of age macrophage-filled sinusoids compress the hapatocytes and the hepatic architecture is disrupted

enlarged liver ( J:63197 )

renal/urinary system

abnormal renal glomerular capsule morphology ( J:63197 )

• finely vacuolated cells, which stain PAS-negative, are found within the Bowman capsule in the glomeruli

abnormal renal tubule epithelium morphology ( J:63197 )

• renal tubular epithelium is diffusely vacuolated

nervous system

demyelination ( J:63197 )

• unlike mice homozygous for only the twitcher mutation, the central nervous system shows normal myelination with rare infiltration of globoid cells at 35-40 days of age but progressively more common at 77 and 94 days of age and the sciatic nerve pathology at 94 days of age is similar to that of 35 to 40 day old twitcher controls

• although the central nervous system maintains myelination, the peripheral nervous system shows distinct demyelination

homeostasis/metabolism

abnormal lipid level ( J:63197 )

• massive lactosylceramide accumulation in brain, kidney, and liver due to a block in lactosylceramide degradation, a reduction to 50-60% of normal levles of galactosylceramide in the kidney and brain, and drastic reduction of brain psychosine levels

growth/size/body

enlarged liver ( J:63197 )

enlarged spleen ( J:63197 )

• macrophage infiltration in the lymph follicles of the spleen at 94 days of age

Genotype
MGI:4452613

cx4

• Allelic Composition: Galc^twi/Galc^twi; Glb1^tm1Adz/Glb1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * CE/J

mortality/aging

premature death ( J:63197 )

• average lifespan is 37.7 days and nearly all die before 46 days of age

behavior/neurological

induced hyperactivity ( J:63197 )

• between 30 and 35 days of age mice are extremely hyper-responsive in response to touching the cage or lifting the lid

seizures ( J:63197 )

• between 30 and 35 days of age the hyper-reactivity can include generalized seizures

nervous system

seizures ( J:63197 )

• between 30 and 35 days of age the hyper-reactivity can include generalized seizures

neurodegeneration ( J:63197 )

• at 27 days of age many dying neurons with deeply eosinophilic cytoplasm and pyknotic nuclei are present diffusely in the cerebral cortex where activated astrocytes and microglia/macrophages are found

• neuronal degeneration of the hippocampus is most pronounced in CA3 and the subiculum and scattered necrotic cells are also found in the hypothalamus, amygdala, caudate/putamen and lateral septal nuclei

• cerebral cortex and to a lesser extent the white matter have activated astrocytes and microglia/macrophages with many dying cells present

demyelination ( J:63197 )

immune system

immune system phenotype ( J:63197 )

N • spleen is free of pathology

liver/biliary system

liver/biliary system phenotype ( J:63197 )

N • liver is free of pathology

homeostasis/metabolism

abnormal lipid level ( J:63197 )

• at 30 and 40 days of age psychosine is significantly elevated in the brain