Analysis Tools
behavior/neurological
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• in a hidden platform Morris water maze assay, mice spend less time in the target quadrant during the acquisition trials, and consistently use longer swimming paths to reach the hidden platform
• however, behavior during training is similar to that in wild-type controls
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• at 4 months of age, mice show difficulty in locating the water source when moved between different types of cages
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• although grip strength is normal, mice are unable to learn to balance and spend less time on an accelerating rotarod
• however, no ataxia is observed, as swimming velocity and endurance in the water maze are normal
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• at 4 months of age, mice display reduced cage activity as determined by the number of light beam crossings within a 24-hr period
• however, neither ambulatory nor qualitative exploratory measures are altered in the open field test
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nervous system
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• although stimulation with 900 AP/10 Hz increases the number of SVs with diameters >60nm in both groups, mutant resting synapses contain larger organelles more often than wild-type
• at rest, SVs from mutant hippocampal neurons are enlarged with diameters of ~41nm versus ~38nm in controls, and appear more heterogenous
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• electron micrographs of hippocampal boutons revealed that mutant resting synapses contain only ~135 SVs per um2 versus ~230 SVs per um2 in wild-type synapses
• after depletion of the SV pool via stimulation with 900 AP/10 Hz, mutant SV numbers are reduced to only ~47 SVs per um2 versus ~105 SVs in wild-type synapses
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• at rest, SV numbers of visibly docked SVs per 100-nm active zone are already reduced by 40% in mutant synapses relative to controls
• upon stimulation (900 AP/10 Hz), SV numbers of visibly docked SVs per 100-nm active zone are reduced by 60% in mutant synapses versus only 28% in controls
• in mutant synapses, SVs numbers within a distance of 20 nm to the active zone are reduced to degrees similar to those of docked SVs after stimulation
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• mice display impaired recycling and acidification of synaptic vesicles in neonatal hippocampal boutons
• SV recycling analysis using synaptopHluorin (an exo- and endocytosis probe) revealed that weak stimulation of SV exocytosis by 100 APs at 20 Hz resulted in a slight delay in the acidification of endocytosed structures; this is increased by stimulations by 300 Aps at 10 Hz
• after complete depletion of the total recycling SV pool, only 46.5% of exocytosed vesicles become re-available for release relative to 94% in wild-type controls
• in addition, SV reformation is incomplete reaching only 70% of that in wild-type hippocampal neurons
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adipose tissue
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• adult mice show loss of interscapular and other subcutaneous adipose tissues
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• CT scan revealed a ~19 reduction in total adipose tissue volume
• within the body, degree of reduction varies between the different types of adipose tissue
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• mice exhibit altered sorting of sortilin in adipocytes leading to inhibition of adipogenesis and lipodystrophy
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• ex vivo, primary MEFs isolated from E12.0 mutant embryos show a 65% reduction in adipogenic differentiation relative to wild-type MEFs, as revealed by Red O lipid staining
• vascular stromal stem cells isolated from mutant epididymal adipose tissue show significantly impaired adipogenic differentiation relative to wild-type cells (3.6% vs 6%)
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• some mice show complete loss of interscapular adipose tissue, resulting in a hump-like appearance
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• at 5 months of age, mice exhibit severe lipodystrophy of subcutaneous adipose tissues
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growth/size/body
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• at 5 months of age, mice are 15% lighter than wild-type controls
• however, no differences in body weight are noted between 4 and 14 weeks of age, irrespective of diet
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cellular
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• ex vivo, primary MEFs isolated from E12.0 mutant embryos show a 65% reduction in adipogenic differentiation relative to wild-type MEFs, as revealed by Red O lipid staining
• vascular stromal stem cells isolated from mutant epididymal adipose tissue show significantly impaired adipogenic differentiation relative to wild-type cells (3.6% vs 6%)
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integument
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• adult mice show loss of interscapular and other subcutaneous adipose tissues
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homeostasis/metabolism
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N |
• mice show no differences in glucose serum homeostasis in a glucose-tolerance assay relative to wild-type controls
• serum levels of IGF-1 and of adipokines (adiponectin, leptin, resisting) are normal
• respiratory coefficient is unaffected
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endocrine/exocrine glands
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N |
• mammary gland development is relatively unaffected as shown by milk duct histology at 4 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| syndromic X-linked intellectual disability 5 | DOID:0060800 |
OMIM:304340 |
J:218588 | |
