Analysis Tools
mortality/aging
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• most homozygotes die before P3
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• less than 8% of homozygotes are obtained at postnatal day 1 (P1)
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nervous system
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• at P1, homozygotes frequently exhibit intracerebral hemorrhage
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• at E12.5 and E15.5, homozygotes display protrusions of forebrain tissue with variable severity, consistent with an increased number of BrdU-positive cells noted in expanded forebrain cortical structures
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hydrocephaly
(
J:49087
)
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• at P1, mutant brains display a marked expansion of the ventricular zone, consistent with an increased number of BrdU-positive cells noted at E12.5 and E15.5
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• at P1, mutant lateral ventricles commonly appear to be contiguous with the subdural space through breaks in the dorsal cortex
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• at P1, mutant brains exhibit loss of commissural structures
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• at P1, mutant brains exhibit absence of the corpus callosum
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• at P1, mutant brains exhibit necrotic and occasionally ectopic tissue along the anterior aspect of cerebral hemispheres, with disrupted bone matrix growing around these masses
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• at P1, mutant newborns exhibit severe cortical disruption resulting in loss of commissural structures; sites of ectopic cortical growth are frequently observed
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cellular
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• rare mutant ES cells that die following UV irradiation exhibit incomplete chromatin condensation
• rare mutant thymocytes that die following dexamethasone treatment show normal apoptotic features, including changes to phosphatidyl serine (PS) on the plasma membrane and chromatin condensation
• in contrast, mutant splenocytes that die in response to UV or gamma irradiation exhibit normal PS plasma membrane changes but aberrant chromatin condensation
• notably, caspase processing is inhibited in mutant ES cells but not in thymocytes or splenocytes
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• homozygous mutant ES cells are resistant to various apoptotic stimuli, including adriamycin, UV and gamma-irradiation, etoposide, sorbitol, cisplatinum, and anisomycin
• mutant MEFs are resistant to apoptosis induced by UV and gamma irradiation, adriamycin, and etoposide
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• homozygous mutant ES cells, embryonic fibroblasts, and thymocytes are resistant to gamma irradiation-induced apoptosis
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• mutant thymocytes are resistant to etoposide-, dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation, anti-CD95, TNF, heat shock, and sorbitol
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• mutant splenocytes are resistant to gamma irradiation-induced apoptosis but are sensitive to other apoptotic stimuli, including UV irradiation, sorbitol, adriamycin, etoposide, and cisplatinum
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• at E12.5, homozygotes display significantly reduced apoptosis in the cerebral cortex and trigeminal ganglion
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• resting mutant thymocytes exhibit a reduced mitochondrial membrane potential relative to wild-type thymocytes
• upon dexamethasone treatment, mutant thymocytes fail to exhibit total loss and retain an abnormally low mitochondrial membrane potential relative to wild-type thymocytes
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cardiovascular system
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• at P1, homozygotes frequently exhibit intracerebral hemorrhage
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growth/size/body
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• at birth, homoygotes are consistently smaller than wild-type pups
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immune system
| N |
• homozygotes exhibit no significant differences in % of various thymocyte, splenocyte, and lymph node subpopulations relative to wild-type mice
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• mutant thymocytes are resistant to etoposide-, dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation, anti-CD95, TNF, heat shock, and sorbitol
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• mutant splenocytes are resistant to gamma irradiation-induced apoptosis but are sensitive to other apoptotic stimuli, including UV irradiation, sorbitol, adriamycin, etoposide, and cisplatinum
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hematopoietic system
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• mutant thymocytes are resistant to etoposide-, dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation, anti-CD95, TNF, heat shock, and sorbitol
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• mutant splenocytes are resistant to gamma irradiation-induced apoptosis but are sensitive to other apoptotic stimuli, including UV irradiation, sorbitol, adriamycin, etoposide, and cisplatinum
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endocrine/exocrine glands
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• mutant thymocytes are resistant to etoposide-, dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation, anti-CD95, TNF, heat shock, and sorbitol
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