Analysis Tools
mortality/aging
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• although born at normal Mendelian ratios, most mice die within 6 weeks after birth
• surprisingly, a few mice survive more than 1 year
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growth/size/body
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• teeth are formed but fail to erupt, unlike in wild-type controls
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nervous system
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• at 4 weeks of age, mice show strong PAS staining in CA3 neurons, unlike wild-type controls
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• at P21, electron-dense osmiophilic material accumulates in lysosomal compartments of pyramidal neuronal somata in the CA3, but not in the CA1 region
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• mice show a nearly complete loss of CA3 pyramidal cells by 10 months of age
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• at 4 weeks of age, mice show increased lysosomal acid phosphatase activity in the cortex relative to wild-type controls
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• neurogeneration in the hippocampus is progressive but significantly delayed relative to null mice and only observed in the few surviving older mice
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• neuronal cell loss within the hippocampal CA3 region is observed at 5 months and progresses to a nearly complete loss of CA3 pyramidal cells by 10 months of age
• no hippocampal cell loss is detected at 4 weeks of age, unlike in null homozygotes
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cellular
| N |
• at 3 weeks of age, mice show no significant increase in the autophagic marker LC3-II in the brain, unlike in null mice or Clcn7tm4.1Tjj homozygotes
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• at 4 weeks of age, lysosomal storage is shown by intracellular carbohydrate accumulation in CA3 neurons and increased lysosomal acid phosphatase activity in the cortex
• at 3 weeks of age, lysosomal storage material is detected in CA3 pyramidal neuron somata
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• lysosomal chloride ion concentration is reduced relative to that in wild-type lysosomes
• however, lysosomal pH is unchanged in fibroblasts
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skeleton
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• teeth are formed but fail to erupt, unlike in wild-type controls
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• mice exhibit a partially deranged ruffled border membrane: 20% of osteoclasts completely lack a ruffled border, and only ~40% show a mature ruffled border, similar to what is observed in null mice
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• mice show increased bone volume fraction of proximal tibia metaphyseal trabecular bone, similar to what is observed in null mice
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• at 3 weeks of age, mice exhibit severe osteopetrosis (of tibiae), similar to that observed in null mice or Ostm1gl homozygotes
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homeostasis/metabolism
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• lysosomal chloride ion concentration is reduced relative to that in wild-type lysosomes
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hematopoietic system
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• mice exhibit a partially deranged ruffled border membrane: 20% of osteoclasts completely lack a ruffled border, and only ~40% show a mature ruffled border, similar to what is observed in null mice
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immune system
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• mice exhibit a partially deranged ruffled border membrane: 20% of osteoclasts completely lack a ruffled border, and only ~40% show a mature ruffled border, similar to what is observed in null mice
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craniofacial
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• teeth are formed but fail to erupt, unlike in wild-type controls
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pigmentation
| N |
• surprisingly, mice display brown fur on an agouti background; hair shaft pigmentation is unchanged relative to that in wild-type controls
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vision/eye
| N |
• mice show no evidence of retinal degeneration up to 10 months of age, unlike in null mice or Clcn7tm4.1Tjj homozygotes
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