Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Eif2ak3tm1Dron mutation
(1 available);
any
Eif2ak3 mutation
(51 available)
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mortality/aging
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• died in the first few days of life
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Eif2ak3tm1Dron mutation
(1 available);
any
Eif2ak3 mutation
(51 available)
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cellular
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• expression of unfolded protein response target genes (Hspa5, Ddit3, Edem, Dnajc3a, Wars, Ero1lb and Pdia4) is decreased in mouse embryonic fibroblasts stressed with tunicamycin or thapsigargin results
• mouse embryonic fibroblast cells are profoundly deficient in their recovery from dithiothreitol realtive to wild-type cells
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Eif2ak3tm1Dron mutation
(1 available);
any
Eif2ak3 mutation
(51 available)
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mortality/aging
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• about half the expected number of homozygous mice were recovered at weaning
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growth/size/body
homeostasis/metabolism
digestive/alimentary system
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• increased cell death in the exocrine pancreas
• the endoplasmic reticulum (ER) in the exocrine pancreas was segmented instead of organized into long, thin, densely packed cisterna and its lumen was distended with material of higher electron density than the contents of wildtype ER
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• observed in most homozygotes by 6-8 weeks of age
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• resulted from pancreatic maldigestion
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endocrine/exocrine glands
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• increased cell death in the exocrine pancreas
• the endoplasmic reticulum (ER) in the exocrine pancreas was segmented instead of organized into long, thin, densely packed cisterna and its lumen was distended with material of higher electron density than the contents of wildtype ER
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• observed occasional cells with striking, abundant, and dilated membrane-bounded cisterna filled with a dense content and these cells generally had fewer secretory granules
• with time, size of islets decreased
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• with time, proportion of glucagon-positive cells increased and they were found to populate the core of the islet as well as its mantle
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• with time, the mass of insulin-producing cells diminished
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• increased levels of endoplasmic reticulum stress in the pancreas
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• observed in most homozygotes by 6-8 weeks of age
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• increased glucose-induced proinsulin biosynthesis in islets of Langerhans, however processing of proinsulin was normal
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Allelic
Composition |
Eif2ak3tm1Dron/Eif2ak3+
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Genetic
Background |
either: 129S6/SvEvTac-Eif2ak3tm1Dron or (involves: 129S6/SvEvTac * C57BL/6) |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Eif2ak3tm1Dron mutation
(1 available);
any
Eif2ak3 mutation
(51 available)
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mortality/aging
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• pups die around P12 regardless whether dams received doxycycline to the end of gestation or until E14
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mortality/aging
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• greater than 90% of animals die by postnatal day 27
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growth/size/body
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• pups are significantly smaller than controls littermates when doxycycline treatment is stopped on E14
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nervous system
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• >60% of animals display tonic seizures
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• in cervical spinal cord at P14, number of apoptotic oligodendrocytes is significantly greater than in controls when doxycycline treatment is stopped at E14
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• in cervical spinal cord at P14, number of apoptotic oligodendrocytes is significantly greater than in controls when doxycycline treatment is stopped at E14
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• when doxycycline treatment is stopped at E14, very few oligodendrocytes are detected in corpus callosum and cerebellum at P14
• if mice are treated with doxycycline until they reach maturity (4 weeks) and then are released from doxycycline, oligodendrocyte survival is unaffected
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• >80% of axons are unmyelinated compared to 30% of spinal cord axons in double mutants on a wild-type Eif2ak3 background when doxycycline treatment is stopped at E14; in mice continuously receiving doxycycline treatment, <10% of spinal cord axons are unmyelinated
• if mice are treated with doxycycline until they reach maturity (4 weeks) and then are released from doxycycline, normal myelin is observed in the central nervous system
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• level of myelin in CNS is significantly reduced at P14 compared to double transgenic mice with wild-type Eif2ak3
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behavior/neurological
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• severe tremors are observed
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• >60% of animals display tonic seizures
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cellular
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• in cervical spinal cord at P14, number of apoptotic oligodendrocytes is significantly greater than in controls when doxycycline treatment is stopped at E14
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• in cervical spinal cord at P14, number of apoptotic oligodendrocytes is significantly greater than in controls when doxycycline treatment is stopped at E14
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Analysis Tools
