Phenotypes associated with this allele

• Allele Symbol: Fuca1^tm1Tlub
• Allele Name: targeted mutation 1, Torben Lubke
• Allele ID: MGI:6118143
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fuca1^tm1Tlub/Fuca1^tm1Tlub	involves: 129S2/SvPas * C57BL/6	MGI:6188994

Genotype
MGI:6188994

hm1

• Allelic Composition: Fuca1^tm1Tlub/Fuca1^tm1Tlub
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

behavior/neurological

impaired contextual conditioning behavior ( J:235359 )

• mice show decreased freezing behavior during the context phase, indicating impaired contextual fear memory

impaired cued conditioning behavior ( J:235359 )

• presentation of the auditory stimulus elicits a very weak or no increase in freezing behavior during the cue phase, indicating impaired cued fear memory

tremors ( J:235359 )

• mice develop a massive tremor after 6 months of age

ataxia ( J:235359 )

• mice become ataxic from 6 months of age

impaired coordination ( J:235359 )

• mice show progressive impairment on the rotarod between 3 and 7 months of age, with decreased drop latencies compared to wild-type mice

decreased grip strength ( J:235359 )

• 3 month old mice show reduced forelimb grip strength and recurrent paw misplacement is seen in 40% of mice

• 7 month old mice show a similar reduction in grip strength without further progression and recurrent paw misplacement is seen in 50% of mice

decreased locomotor activity ( J:235359 )

• mice become progressively inactive from 6 months of age, avoiding any type of movement

cellular

abnormal lysosome morphology ( J:235359 )

• mice exhibit translucent cytoplasmic vacuoles in most tissues examined at 5-9 months of age and lysosomal accumulation of fucosylated glycoasparagine molecules in various tissues

• in the liver, Kupffer cells and sinusoidal endothelial cells exhibit large empty vacuoles while hepatocytes show lower levels of lysosomal storage

• in the kidney, glomerular podocytes, glomerular mesangium cells and convoluted proximal tubules exhibit moderate lysosomal storage whereas the intercalated cells of the collecting ducts are severely vacuolated

• the urinary bladder shows large empty vacuoles, particularly in the superficial umbrella cells of the urothelium

• in the spleen, sinusoidal endothelial cells, trabecular fibroblasts, and lymphocytes exhibit lysosomal storage

• storage vacuoles are prominent in the epithelial cells of many other organs such as the pancreas and gall bladder

• in a few cell types such as hepatocytes, principal cells of renal collecting ducts and cells of the convoluted proximal tubules, storage vacuoles contain very homogenous amorphous material of moderate electron density which is different from the empty vacuoles seen in the majority of cells

• lysosomal storage is not seen in bone cells, rental thick ascending limbs of Henles loop, skeletal muscle and heart muscle

• storage vacuoles are prominent in neuronal perikarya, astrocytes, amoeboid micorglia and in the ependymium and choroid plexus epithelium

homeostasis/metabolism

increased brain cholesterol level ( J:235359 )

• accumulation of free cholesterol in the molecular layer of the cerebellum in 3 and 11 month old mice

abnormal urine homeostasis ( J:235359 )

• mice exhibit increased excretion of fucosylated glycoconjugates in urine

abnormal enzyme/coenzyme activity ( J:235359 )

• total lack of alpha-L-fucosidase activity

• alpha-mannosidase enzyme activity is elevated

• beta-hexosaminidase activity is increased in spleen, cerebrum, cerebellum, and kidney but is normal in the liver

nervous system

increased brain cholesterol level ( J:235359 )

• accumulation of free cholesterol in the molecular layer of the cerebellum in 3 and 11 month old mice

Purkinje cell degeneration ( J:235359 )

• age-dependent decrease of Purkinje cells from 3.5 months to 7.5 months, leading to a nearly complete loss of Purkinje cells at 11 months of age

• however, mice do not exhibit myelination defects in the CNS

brain vacuoles ( J:235359 )

• storage vacuoles are prominent in neuronal perikarya, astrocytes, amoeboid micorglia and in the ependymium and choroid plexus epithelium

• GM2 ganglioside is prominent in vesicular structures of the CA3 region of the hippocampus, the cerebral cortex and in the molecular layer of the cerebellum

• - autofluorescent storage material in cerebrum and cerebellum of 11 month old mice, primarily in the molecular layer

astrocytosis ( J:235359 )

axonal spheroids ( J:235359 )

• axon spheroids are seen in gray matter and among the perikarya of the nucleus gracilis and in the white matter

• axoplasm in the spheroids is crowded with disoriented neurotubules, neurofilaments, and heterogenous material

pigmentation

lipofuscinosis ( J:235359 )

• the molecular layer of the cerebellum is positive for lipofuscin (aggregates of oxidized proteins, lipids, and metal ions)

renal/urinary system

enlarged urinary bladder ( J:235359 )

• urinary bladders, particularly of males, are increased in size at 6 months of age, with an overall volume of 2-3 ml instead of 0.15-0.25 ml in wild-type mice however, urinary creatinine concentration is normal

abnormal urine homeostasis ( J:235359 )

• mice exhibit increased excretion of fucosylated glycoconjugates in urine

growth/size/body

enlarged urinary bladder ( J:235359 )

• urinary bladders, particularly of males, are increased in size at 6 months of age, with an overall volume of 2-3 ml instead of 0.15-0.25 ml in wild-type mice however, urinary creatinine concentration is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fucosidosis		DOID:14500	OMIM:230000	J:235359