Analysis Tools
mortality/aging
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• some mice, including animals with combinations of most or all defects do survive to adulthood and reproduce
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• severity of defects results in death at or shortly after birth
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• severity of defects results in death shortly after birth; preweaning lethality is 6%
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cardiovascular system
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• in some foci of proliferation, rupture of blood vessels occurs, causing hemorrhages into parenchyma of cerebral hemispheres
• by E17.5, massive hemorrhage in brain and subectodermal tissue of the frontal bulges can be seen through the skin
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craniofacial
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• in mutant embryos with facial clefts observed at E16.5-17.5, skulls are flat due to absence of cephalic flexure in rostrally extended brain
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• show normal sutures, but one to three round holes up to 3 mm in diameter) mark sites where ossification had been impaired by enlarged forebrain
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• affected animals exhibit usually bilateral bumps over the forehead; bumps may be larger on one side or give the appearance of a wholly enlarged forehead
• in adult mice, bumps usually contain loose connective tissue
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short snout
(
J:41353
)
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• affected animals may show shorter snouts
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• a few embryos exhibit facial clefting at E12 and later; mutant embryos observed at E16.5-17.5 display herniation of entire forebrain through middle of face
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limbs/digits/tail
curly tail
(
J:41353
)
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• around 50% of mutants may display curly or looped tails, shaped like a corkscrew; may be present singly (20%) or in combination with exencephaly and/or spina bifida (40%)
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kinked tail
(
J:41353
)
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• tails are malformed in about half of the mutants; tails may show distal kinks
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nervous system
| N |
• in adult animals, neuronal counts of spinal and cranial motoneurons, spinal interneurons, dorsal root ganglion sensory neurons, and superior cervical ganglion sympathetic neurons are not different from wild-type
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• in some foci of proliferation, rupture of blood vessels occurs, causing hemorrhages into parenchyma of cerebral hemispheres
• by E17.5, massive hemorrhage in brain and subectodermal tissue of the frontal bulges can be seen through the skin
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• some cell death is observed in lesions of telencephalic walls at E10.5
• cells are less densely packed and protrude slightly into lumen of lateral ventricle
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• at E10.5, cranial neuropore is still open whereas it is closed in wild-type embryos; closure in essentially all mutants is observed at E12.5
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spina bifida
(
J:131954
)
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• animals also display mild-to-moderate lumbar spina bifida
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• spina bifida is observed in some pups, sometimes as an opening in the lumbar region, or healed but still visible as a small scar; may be present singly (40%) or in combination with exencephaly and/or tail defects (20%)
• persistent caudal neuropore occurs separately from tail deflections in 60% of affected animals
• lumbo-sacral neural tube defects observed in about half the animals are secondarily closed during late gestation and remain visible as small wound on dorsal aspect of sacral region in newborns
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• absence of cephalic flexure in rostrally extended brain
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• at E13.5-14.5, mass of forebrain tissue has increased due to hemorrhage and multifocal proliferation such that cerebral hemispheres are starting to bulge from surface of head; by E17.5, forebrain tissue mass compressed overlying subepidermal mesenchyme
• in embryos (E17.5), herniation of forebrain tissue may be observed; forebrain is enlarged
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• at E10.5, telencephalic walls are folded in embryos with open cranial neuropore
• lesions of telencephalic walls are detected at E10.5
• cells of walls extrude outwardly, compressing connective tissue of meninges and subepidermal mesenchyme which will form calvaria; such extrusions are observed extending into mesenchyme around basal forebrain and sometimes penetrate wall of the pharynx
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• at E10.5, embryos with open cranial neuropore display collapsed lateral ventricles
• cells of telencephalic walls are less densely packed than in wild-type and protrude slightly into lumen of lateral ventricle at E10.5; at E12.5, protrusions are more conspicuous with more cells and vascularization
• lumen of ventricles are narrower than wild-type at E12.5; ventricles often contain blood
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• at E13.5 and E14.5, cerebral hemispheres show many folds and intraparenchymal proliferation foci
• mesenchymal and epidermal cover of hemispheres is extremely thin on top
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• mutants show exencephaly or herniation of the forebrain; may be present singly or in combination with tail defects and/or spina bifida
(J:41353)
• forebrain exencephaly is observed, similar to other Apaf1-null mutants
(J:131954)
• in adult homozygotes, exencephalic forebrain is covered by skin and hair an appears as forehead bumps
(J:131954)
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reproductive system
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• some adult females breed poorly or do not reproduce
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• some adult males breed poorly or do not reproduce
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skeleton
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• in mutant embryos with facial clefts observed at E16.5-17.5, skulls are flat due to absence of cephalic flexure in rostrally extended brain
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• show normal sutures, but one to three round holes up to 3 mm in diameter) mark sites where ossification had been impaired by enlarged forebrain
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• spina bifida is observed in some pups, sometimes as an opening in the lumbar region, or healed but still visible as a small scar; may be present singly (40%) or in combination with exencephaly and/or tail defects (20%)
• persistent caudal neuropore occurs separately from tail deflections in 60% of affected animals
• lumbo-sacral neural tube defects observed in about half the animals are secondarily closed during late gestation and remain visible as small wound on dorsal aspect of sacral region in newborns
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embryo
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• some cell death is observed in lesions of telencephalic walls at E10.5
• cells are less densely packed and protrude slightly into lumen of lateral ventricle
|
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• at E10.5, cranial neuropore is still open whereas it is closed in wild-type embryos; closure in essentially all mutants is observed at E12.5
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spina bifida
(
J:131954
)
|
• animals also display mild-to-moderate lumbar spina bifida
|
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• spina bifida is observed in some pups, sometimes as an opening in the lumbar region, or healed but still visible as a small scar; may be present singly (40%) or in combination with exencephaly and/or tail defects (20%)
• persistent caudal neuropore occurs separately from tail deflections in 60% of affected animals
• lumbo-sacral neural tube defects observed in about half the animals are secondarily closed during late gestation and remain visible as small wound on dorsal aspect of sacral region in newborns
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growth/size/body
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• affected animals exhibit usually bilateral bumps over the forehead; bumps may be larger on one side or give the appearance of a wholly enlarged forehead
• in adult mice, bumps usually contain loose connective tissue
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short snout
(
J:41353
)
|
• affected animals may show shorter snouts
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• a few embryos exhibit facial clefting at E12 and later; mutant embryos observed at E16.5-17.5 display herniation of entire forebrain through middle of face
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