Analysis Tools
mortality/aging
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• premature death of around 3 weeks of age is seen in some mice
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behavior/neurological
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N |
• unprovoked clinical seizures are not seen
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homeostasis/metabolism
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• unesterified cholesterol is detected in cells of the basolateral amygdala which is not seen in wild-type neurons
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• GM2 ganglioside accumulation, particularly in the basolateral nuclei of the amygdala, occurs specifically in late endosomes and lysosomes
• GM2 ganglioside accumulation in neurons is more prominent in homozygous females than in hemizygous males
• by 12 weeks of age, GM2 accumulation is also seen in neurons of CA3 and CA4 regions and the inner dentate gyrus of the hippocampus, as well as hypothalamus, fasciola cinereum, and piriform cortex
• however, accumulation of GM1, GM3 or GD3 gangliosides in the brain is not seen
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• no active beta-hexosaminidase enzyme activity, the lysosomal enzyme responsible for GM2 degradation, is seen in neurons storing GM2 ganglioside
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nervous system
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• small increase in hyperphosphorylated tau are seen in soluble brain fractions
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• unesterified cholesterol is detected in cells of the basolateral amygdala which is not seen in wild-type neurons
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• GM2 ganglioside accumulation in late endosomes and lysosomes in the basolateral nuclei of the amygdala
• cholesterol sequestration in neurons of the amygdala
• some amygdala neurons exhibit singular, non-membrane-bound structures resembling aggresomes or one or more membrane-bound lysosomal-like inclusions composed of dense matrix in the cytoplasm
• some neurons in the amygdala exhibit an abnormal distribution of vesicular organalles corralled near the Golgi and trans-Golgi network with other perikaryal regions appearing organelle deficient
• nuclei of neurons in the amygdala are often lobulated excessively and/or multiple number of nucleoi are seen
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• some neurons in the cerebral cortex exhibit an abnormal distribution of vesicular organelles corralled near the Golgi and trans-Golgi network with other perikaryal regions appearing organelle deficient
• however, cerebral cortex and subcortical regions do not show evidence of lysosomal storage
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• increase in the number of lysosomes in neurons storing GM2 ganglioside
• cholesterol and GM2 ganglioside sequestration occurs in the same neurons of the amygdala, but the two substrates are segregated to different subcellular vesicular populations
• the cytoplasm of some amygdala neurons exhibits singular, non-membrane-bound structures resembling aggresomes or one or more membrane-bound lysosomal-like inclusions composed of a dense matrix
• some neurons in the amygdala and cerebral cortex exhibit an abnormal distribution of vesicular organelles corralled near the Golgi and trans-Golgi network with other perikaryal regions appearing organelle deficient
• neurons with GM2 ganglioside storage contain multiple, large loose-lamellar vesicles resembling storage bodies
• nuclei of neurons in the amygdala and elsewhere are often lobulated excessively and/or multiple number of nucleoi are seen
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• extensive and progressive loss of Purkinje cells in the cerebellum
• loss of Purkinje cells occurs in a regular pattern of parasagittal stripes in the cerebellar vermis and hemispheres
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• presence of Purkinje cell axonal spheroids
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Christianson syndrome | DOID:0060825 |
OMIM:300243 |
J:241124 | |
