Analysis Tools
cellular
 |
• under basal conditions, primary mouse embryonic fibroblasts (MEFs) isolated from E13.5 mutant embryos show a markedly dilated ER lumen relative to wild-type MEFs
• lysosome morphology is normal under basal conditions
• exposure to thapsigargin causes the ER of mutant MEFs to dilate and fragment to a similar extent as in wild-type MEFs
|
|
|
• mutant MEFs show increased sensitivity to ER stress-induced apoptosis relative to wild-type MEFs
• after treatment with thapsigargin or tunicamycin, mutant MEFs show increased apoptotic markers, including cleaved caspase 3 and PARP, relative to wild-type MEFs
• however, mutant MEFs show normal sensitivity to VP16-induced or Fas ligand-induced apoptotic pathways
|
|
|
• in a neonatal hypoxic-ischemic brain injury model, hemizygous males show markedly increased neuron apoptosis in the hippocampi ipsi-lateral to the common carotid artery ligation relative to wild-type controls
• after treatment with tunicamycin, cultured primary cortical neurons isolated from E16.5 mutant embryos show increased neuronal death relative to wild-type neurons
• after transient exposure to potassium cyanide/2-deoxyglucose followed by recovery (to mimic ischemia-reperfusion injury in culture), mutant cortical neurons show a significant increase in cell death relative to wild-type neurons
• however, mutant cortical neurons show normal sensitivity to staurosporine (STS)-induced cell death
|
|
|
• under basal conditions, mutant MEFs exhibit an increased level of specific ER stress markers relative to wild-type MEFs, as shown by the increased cleavage of caspase 12 and slight induction of GRP78
• after treatment with thapsigargin or tunicamycin, mutant MEFs show increased levels of cleaved caspase 12 and GRP78 relative to wild-type MEFs
|
|
|
• mutant MEFs exhibit delayed ER-Golgi trafficking in an ER trafficking assay
|
nervous system
|
|
• in a neonatal hypoxic-ischemic brain injury model, hemizygous males show markedly increased neuron apoptosis in the hippocampi ipsi-lateral to the common carotid artery ligation relative to wild-type controls
• after treatment with tunicamycin, cultured primary cortical neurons isolated from E16.5 mutant embryos show increased neuronal death relative to wild-type neurons
• after transient exposure to potassium cyanide/2-deoxyglucose followed by recovery (to mimic ischemia-reperfusion injury in culture), mutant cortical neurons show a significant increase in cell death relative to wild-type neurons
• however, mutant cortical neurons show normal sensitivity to staurosporine (STS)-induced cell death
|
|
|
• in a neonatal hypoxic-ischemic brain injury model, hemizygous males show a ~10-fold increase in the volume of hippocampal injury (55%) relative to wild-type controls (5%) as well as markedly increased apoptosis in the ipsi-lateral hippocampi, as shown by TUNEL staining
|
homeostasis/metabolism
|
|
• in a neonatal hypoxic-ischemic brain injury model, hemizygous males show a ~10-fold increase in the volume of hippocampal injury (55%) relative to wild-type controls (5%) as well as markedly increased apoptosis in the ipsi-lateral hippocampi, as shown by TUNEL staining
|
