mortality/aging
• homozygous embryos decrease in number between E15 and birth with <10% surviving birth and immediate postnatal period
|
• few mutants survive to weaning, likely due to feeding impairment due to craniofacial abnormalities as well as neurological problems
|
embryo
• by E10, embryos show growth retardation
|
• by E10, some embryos show neural tube defects, including craniofacial defects, myelomeningoceles and encephaloceles; some of these defects are observed in live-born mutants
|
• by E10, some embryos display myelomeningoceles
|
• areas of colliquative necrosis are seen at birth containing foamy and debris-laden macrophages
|
growth/size/body
• majority of mutants have abnormal dentition
|
• by E10, embryos show growth retardation
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• all late embryonic and live-born pups are severely runted
|
nervous system
• within necrotic brain areas, petechial hemorrhage containing macrophages and ingested erythrocytes is observed
|
• by E10, some embryos show neural tube defects, including craniofacial defects, myelomeningoceles and encephaloceles; some of these defects are observed in live-born mutants
|
• by E10, some embryos display myelomeningoceles
|
• brains are smaller than wild-type or heterozygous littermates
|
• adjacent to necrotic areas of cerebral cortex, lateral ventricles are enlarged
|
• cerebral cortex and subcortical white matter display necrosis; white matter demonstrates rarefaction and microcystic changes
|
exencephaly
(
J:118880
)
• seen in some embryos by E10
|
• by E10, some embryos display encephaloceles
|
behavior/neurological
craniofacial
• embryos and pups have absent calcification of the cranium
|
• majority of mutants have abnormal dentition
|
• majority of late embryonic and live born mutants show doming of cranium
|
skeleton
• embryos and pups have absent calcification of the cranium
|
• majority of mutants have abnormal dentition
|
• majority of late embryonic and live born mutants show doming of cranium
|
• by E10, some embryos display myelomeningoceles
|
• deficient calcification of the diaphseal portion of the long bones is observed in embryos an neonates
|
cardiovascular system
hemorrhage
(
J:118880
)
• most embryos display large areas of hemorrhage in craniofacial, cervical and dorsal aspects of trunk
|
• within necrotic brain areas, petechial hemorrhage containing macrophages and ingested erythrocytes is observed
|
hematopoietic system
• mutant T lymphocytes from thymus and peripheral lymph nodes of recipients of mutant liver cells show defective response to receptor-dependent and -independent stimulation
• addition of exogenous Il-2 restores proliferative capacity
|
• T lymphocytes developing from mutant liver cells in recipient mice show reduced numbers of secretory vesicles compared to wild-type lymphocytes
|
• transplanted liver hematopoietic progenitor cells show defects
|
• thrombin induced platelet aggregation is diminished compared to wild-type
|
immune system
• mutant T lymphocytes from thymus and peripheral lymph nodes of recipients of mutant liver cells show defective response to receptor-dependent and -independent stimulation
• addition of exogenous Il-2 restores proliferative capacity
|
• T lymphocytes developing from mutant liver cells in recipient mice show reduced numbers of secretory vesicles compared to wild-type lymphocytes
|
homeostasis/metabolism
• transplanted liver hematopoietic progenitor cells show defects
|
• thrombin induced platelet aggregation is diminished compared to wild-type
|
cellular
• mutant T lymphocytes from thymus and peripheral lymph nodes of recipients of mutant liver cells show defective response to receptor-dependent and -independent stimulation
• addition of exogenous Il-2 restores proliferative capacity
|