Analysis Tools
nervous system
astrocytosis
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J:242257
)
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• number of GFAP+ astrocytes are increased starting from 4 months of age in all brain areas studied and increase with age
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• microglia cells containing storage material are most prominent in caudatoputamen and in brain cortex and are first detected at 2 months of age
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microgliosis
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J:242257
)
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• brain tissues show increased levels of activated microglia
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• decrease of total content of coenzyme Q10 in brain tissues of older mice
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• brain shows increased expression of inflammation markers MIP1alpha (CCL3) and TNFA as early as 10 days after birth, with levels increasing to reach maximum at 8 months of age, indicative of progressive neuroinflammation
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• brain shows coarse vacuolization of the cytoplasm of multiple CD68+ cells giving them foam cell-like appearance; these cells disperse in grey and less in white matter, are frequently adjacent to neurons suggesting they are perineuronal microglia
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• neurons have a finely granular appearance of their perikarya and have increased number and size of lysosomes in the brain cortex, thalamus, hypothalamus, amygdala, midbrain, pons, and cerebellum; most prominently in neurons present in deep cortical layers, in hippocampus, and in cerebellum
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• neurons show early mitochondrial structural abnormalities; mitochondria are pleomorphic, increased in number and swollen with disorganized or reduced inner membranes
• mitochondrial network is less organized and the ratio between the fused and single mitochondria is reduced in neurons
• neurons do not have lysosomes containing classical zebra-bodies but some storage deposits contain structures resembling degenerated mitochondria
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• hippocampal neurons show a reduction in density of Syn1+ puncta along the MAP2-stained dendrites as well as of PSD95+ in juxtaposition with VGLUT1+ puncta
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• areas of excitatory post synaptic densities (PSDs) of CA1 neurons are reduced at 6 months of age and at 6 months
• the density of synaptic vesicles is reduced by approximately 30% at 3 months and about 40% at 6 months
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• neuronal loss in the somatosensory cortex starting from 6 months of age such that by 12 months of age, more than a 30% reduction of neural density is seen
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• Purkinje cell loss in the cerebellar cortex is massive in the anterior lobe with lobules I, II, and III most severely affected at 12 months of age
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• neurotransmission is impaired
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• mice show an age-dependent decrease in miniature excitatory postsynaptic current (mEPSC) amplitudes (P14-P20 vs. P45-P60) suggesting progressive synaptic defects
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• decrease in frequency of mEPSCs at P14-P20 and P45-P60
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• decrease in amplitude of mIPSCs at P14-P20 and P45-P60
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• decrease in frequency of mIPSCs at P14-P20 and P45-P60
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adipose tissue
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• reduction in abdominal fat at 11-12 months of age
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behavior/neurological
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• mice need more time to find the hidden platform compared to wild-type mice in the Morris water maze at 10 months of age, but not at 5, 7, or 8 months of age suggesting impaired spatial learning
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• in the probe trail on day 9 of the Morris water maze when the platform is removed, mice spend less time and travel less distance in the target quadrant where the platform used to be located, indicating a decline of spatial memory
• 10-month-old mice show lack of precision with fewer platform crossings in the Morris water maze
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• mice show reduced anxiety in the open field during the light cycle
(J:242257)
• mice show reduced anxiety in the open field test only between 8 and 10 months of age
(J:343336)
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• about 30% of 11-12 month-old mice exhibit spasticity of hind limbs and loss of coordination in a balance test
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• mice show abnormal gait starting at 11-12 months of age
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• mice show increased activity in the open field during the light cycle, however by 10 months of age the signs of hyperactivity diminish
(J:242257)
• mice exhibit higher than average speed and distance traveled in the open field and show increased frequency of crossing the central field and central distance travelled in the open field
(J:242257)
• mice show decreased frequency and duration of periods of immobility in the open field
(J:242257)
• however, mice exhibit normal behavior on the accelerating rotarod
(J:242257)
• mice show hyperactivity in the open field test only between 8 and 10 months of age
(J:343336)
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spasticity
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J:242257
)
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• about 30% of 11-12 month-old mice exhibit spasticity of hind limbs and loss of coordination in a balance test
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cardiovascular system
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• Kupffer cells are increased in number starting from 2 months and become enlarged and stain for cathepsin D at later stages, showing signs of transformation into foam cells
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cellular
astrocytosis
(
J:242257
)
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• number of GFAP+ astrocytes are increased starting from 4 months of age in all brain areas studied and increase with age
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• microglia cells containing storage material are most prominent in caudatoputamen and in brain cortex and are first detected at 2 months of age
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microgliosis
(
J:242257
)
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• brain tissues show increased levels of activated microglia
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• neurons show early mitochondrial structural abnormalities; mitochondria are pleomorphic, increased in number and swollen with disorganized or reduced inner membranes
• mitochondrial network is less organized and the ratio between the fused and single mitochondria is reduced in neurons
• neurons do not have lysosomes containing classical zebra-bodies but some storage deposits contain structures resembling degenerated mitochondria
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• liver tissues and brain show increased levels of LC3-II at all ages tested and at 6 months or older, respectively, indicating increased autophagosomal genesis or decreased macroautophagic flux
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• increase in neuronal levels of subunit C of mitochondrial ATP synthase aggregates and ubiquitin suggestive of mitophagy and a general impairment of proteolysis
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• presence of LC3+ puncta is seen in cortical layer 4-5 pyramidal neurons at 6 months, suggesting an autophagy block
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• medial entorhinal cortex neurons exhibit an increase in levels of O-GlcNAc-modifed proteins indicating endoplasmic reticulum stress
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• lysosomal accumulation of heparan sulphate in multiple cell types, including brain neurons and microglia, hepatocytes, Kupffer cells, splenic sinus endothelial cells, respiratory bronchial epithelium, glomeruli and epithelial cells of distal tubules and collecting ducts, and sparsely in lamina, muscularis propria, and adventitia
(J:242257)
• incipient neuronal storage is detectable in 5-month-old mice, and at the most advanced stages (14-16 months), neuronal lysosomes have massive accumulation of closely packed fibrillary deposits resembling storage material of a rectilinear and/or fingerprint type in neuronal ceroid lipofuscinoses
(J:242257)
• however no signs of lysosomal storage are detected in vascular endothelial cells, in the heart, the eye, and in alveolar septa of lungs
(J:242257)
• mice show increased levels of glycosaminoglycan storage in the brain
(J:343336)
• neurons in cortical layer 4-5 contain increased levels of enlarged autofluorescent ceroid materials at 4 months
(J:343336)
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• mice exhibit reduced mitochondrial respiratory chain enzyme activities in brain cells, with activities of complex IV and complex II enzymes being lower at 8 and 12 months and 8 months, respectively
• activities of complex II, complex II + III, and citrate synthase decrease with age
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growth/size/body
weight loss
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J:242257
)
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• mice show weight loss at 10-12 months of age
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hematopoietic system
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• Kupffer cells are increased in number starting from 2 months and become enlarged and stain for cathepsin D at later stages, showing signs of transformation into foam cells
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• microglia cells containing storage material are most prominent in caudatoputamen and in brain cortex and are first detected at 2 months of age
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microgliosis
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J:242257
)
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• brain tissues show increased levels of activated microglia
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homeostasis/metabolism
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• liver tissues and brain show increased levels of LC3-II at all ages tested and at 6 months or older, respectively, indicating increased autophagosomal genesis or decreased macroautophagic flux
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• increase in neuronal levels of subunit C of mitochondrial ATP synthase aggregates and ubiquitin suggestive of mitophagy and a general impairment of proteolysis
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• presence of LC3+ puncta is seen in cortical layer 4-5 pyramidal neurons at 6 months, suggesting an autophagy block
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• decrease of total content of coenzyme Q10 in brain tissues of older mice
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• glycosaminoglycan levels in brain and liver are increased on average 2-fold and 10-fold, respectively at 12 months of age
(J:242257)
• approximate 2-fold increase in levels of GM2 and GM3 gangliosides in the brain of 4-month-old mice
(J:242257)
• GM2 and GM3 ganglioside storage is seen in most areas of the brain, including the cerebellum, but is most prominent in the deep layers of the cortex and hippocampus
(J:242257)
• mice show increased levels of heparan sulfate-derived deltaDiHS-0S disaccharide in serum, urine, and brain and deltaDiHS-NS disaccharide in the brains indicating increased levels of glycosaminoglycan (GAG) storage
(J:343336)
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• neurons exhibit accumulation of gangliosides, with an increase in the number of ganglioside+ granules in the hippocampal and cerebellar neurons
(J:242257)
• gangliosides accumulate in compartments having lysosomal and non-lysosomal origin
(J:242257)
• brain glycosphingolipid composition is altered, with most drastic changes in GM3 levels, with a 6-fold increase in GM3, 4-fold increase in GM2, and 2-fold increase in GA2 levels in the brain; levels remain similar at all studied ages
(J:343336)
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• activities of lysosomal glycosidases in tissues are either similar or higher than those of wild-type mice and progressively increase with age
• highest increase of lysosomal glycosidase activities is in liver tissues which have approximately 5-fold increase in alpha-galactosidase activity and approximately 20-fold increase of beta-hexosaminidase activity at 6 months of age
• beta-hexosaminidase activity is increased 2-3 fold in the brain, lungs, and kidney
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• mice exhibit reduced mitochondrial respiratory chain enzyme activities in brain cells, with activities of complex IV and complex II enzymes being lower at 8 and 12 months and 8 months, respectively
• activities of complex II, complex II + III, and citrate synthase decrease with age
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immune system
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• Kupffer cells are increased in number starting from 2 months and become enlarged and stain for cathepsin D at later stages, showing signs of transformation into foam cells
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• microglia cells containing storage material are most prominent in caudatoputamen and in brain cortex and are first detected at 2 months of age
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microgliosis
(
J:242257
)
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• brain tissues show increased levels of activated microglia
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• brain shows increased expression of inflammation markers MIP1alpha (CCL3) and TNFA as early as 10 days after birth, with levels increasing to reach maximum at 8 months of age, indicative of progressive neuroinflammation
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• mice show increased presence of inflammatory cells in liver sinusoids
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liver/biliary system
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• liver shows a massive accumulation of vacuoles, either electron-lucent or containing a fine sparse material characteristic of glycosaminoglycan storage in the cytoplasm of hepatocytes and less prominent storage in Kupffer and Ito cells
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• Kupffer cells are increased in number starting from 2 months and become enlarged and stain for cathepsin D at later stages, showing signs of transformation into foam cells
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• hepatocytes in the centrolobular and intermediate zones show microvacuolization of cytoplasm, which becomes more prominent with age
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• early activation of Kupffer cells preceding substantial storage
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• mice show increased presence of inflammatory cells in liver sinusoids
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renal/urinary system
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• due to urinary retention
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skeleton
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• mice show no signs of skeletal abnormalities and no signs of femoral head necrosis
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| mucopolysaccharidosis type IIIC | DOID:0111393 |
OMIM:252930 |
J:242257 , J:343336 | |
