Analysis Tools
mortality/aging
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• all homozygotes die between P21 and P26, with an average lifespan of 23.6 days
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growth/size/body
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• homozygotes are of normal size at E17, but exhibit a reduced body size shortly after birth
• by P18, homozygotes are severely runted relative to wild-type and heterozygous littermates
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weight loss
(
J:83377
)
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• although homozygotes gain weight in the first four time intervals studied (P2-P5, P5-P9, P9-P12, P12-P17), they lose weight at P17-P22, suggesting a reduction in nutrient intake
• at P17-P22, homozygotes become increasingly unhealthy and dependent on solid food, and typically die within 4 days of the last weight measurement (P22)
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• homozygotes display a significantly reduced growth rate throughout their entire lifespan
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behavior/neurological
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• at P20, homozygotes suffer from a lack of nutrient intake, as evidenced by the hepatocellular and myofiber atrophy observed in the absence of other detectable lesions in these tissues
• although homozygotes are physically capable of biting and eating solid food, thay fail to survive on a solid-food diet
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• by P18, homozygotes exhibit a resting tremor in the absence of motor neuron degeneration
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• by P18, homozygotes display severe limb weakness in the absence of motor neuron degeneration
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nervous system
| N |
• in vitro, no significant differences are observed in the growth and morphology of primary neuronal cultures from the cerebral cortex of E16 wild-type and homozygous mutant mice, as determined by neurite outgrowth index, number of neurites per cell, or average neurite length per neuron
• in vivo, analysis of cortical neurons (layers III and IV) and hippocampal neurons (CA1 field) confirmed that neuronal morphogenesis is normal
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• homozygotes exhibit a developmental decrease in the number of cells and/or projections that comprise the cerebral cortex, striatum, and lateral septum
• in contrast, the hypothalamus appears to be neuroanatomically intact
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• by P18, homozygotes display a reduction in overall brain size relative to wild-type and heterozygous littermates
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• at P20, homozygotes display enlarged lateral ventricles along with a reduction in lateral septum size
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• at P20, homozygotes display a reduction in corpus callosum size
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• at P20, homozygotes display a reduction in striatum size
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• by P18, homozygotes display a dramatic reduction in cerebral cortex size; however, all cortical layers are normally present
• other brain regions, including the hippocampus and cerebellum, appear to develop properly
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• at P20, an abnormal reduction of the cingulate gyrus in the retrosplenial cortex underlying the superior colliculus is observed
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• at P20, homozygotes display thinning of the cerebral cortex
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digestive/alimentary system
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• at P20, the villi of small intestines are lengthened relative to those of wild-type controls, indicating that food intake is reduced
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liver/biliary system
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• at P20, mutant hepatocytes show a normal morphology but are smaller than wild-type
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muscle
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• at P20, mutant skeletal muscle shows an apparent increase in the number of nuclei along with a reduction in the size of individual myocytes
• however, no nerve-related changes are observed in skeletal muscle structure
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