Analysis Tools
mortality/aging
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• homozygotes die in utero; resorptions are already present at E10.5-E12.5, suggesting that embryonic lethality may occur prior to these stages
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hematopoietic system
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• homozygotes exhibit a failure of hematopoiesis in liver cultures
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• in some cases, E12.5 homozygotes show an increase in myeloid cell numbers relative to wild-type mice
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• in some cases, E12.5 homozygotes show an increase in liver megakaryocyte levels relative to wild-type mice
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• at E12.5, mutant red cells have more densely stained cytoplasm of reduced volume and pyknotic nuclei that are in some cases irregular
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• homozygotes display abnormal erythrocytes in fetal blood, loss of mature nucleated red cells in the yolk sac vessels, and abnormal proliferation of immature erythrocytes in the liver
(J:2498)
• at E13.5, homozygotes synthesize normal levels of adult beta-globin chains, suggesting normal hemoglobin chain switching; thus, abnormal production of nucleated erythrocytes occurs only during fetal liver erythropoiesis
(J:20542)
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• at E12.5, homozygotes display a lower ratio of red to white blood cells relative to wild-type
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nervous system
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• homozygotes have a more prominent fourth ventricle relative to wild-type mice (variable penetrance)
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• homozygotes display a significantly smaller frontal lobe relative to wild-type embryos (variable penetrance)
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• at E11.5, homozygotes exhibit numerous apoptotic cells in the spinal ganglia, identified by their pyknotic and fragmented nuclei and dense eosinophilic cytoplasm
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• at ~E14.5, homozygous mutant embryos display massive degeneration of the developing CNS
(J:20542)
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craniofacial
flat forehead
(
J:2498
)
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• homozygotes display a compressed forehead relative to wild-type mice (variable penetrance)
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embryo
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• at E12.5, 11 out of 17 mutant embryos resemble wild-type embryos of an earlier embryonic stage, suggesting developmental retardation (variable penetrance)
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pale yolk sac
(
J:2498
)
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• at E12.5, 11 out of 17 homozygotes have a pale appearance (variable penetrance)
• mutant yolk sac membranes are thinner with empty capillaries and fewer red cells relative to wild-type
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cellular
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• at E11.5, mutant embryos exhibit increased apoptosis in the spinal cord, myelencephalon, pontine flexure, and particularly in the spinal ganglia; in 1 out of 17 embyos, degeneration extends into the prosencephalon
• increased cell death is specifically noted in the intermediate zone (but not in the ventriculate zone) with ectopic mitosis
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growth/size/body
flat forehead
(
J:2498
)
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• homozygotes display a compressed forehead relative to wild-type mice (variable penetrance)
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• at E12.5, 11 out of 17 mutant embryos resemble wild-type embryos of an earlier embryonic stage, suggesting developmental retardation (variable penetrance)
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liver/biliary system
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• at E11.5, mutant livers show abnormal trabecular structure with dilated sinusoids containing red cells, some of which are irregular and some apoptotic
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• the mutant fetal liver displays reduced cellularilty relative to wild-type
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immune system
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• in some cases, E12.5 homozygotes show an increase in myeloid cell numbers relative to wild-type mice
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vision/eye
| N |
• in homozygotes, retinal development occurs normally at least until E14.5
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• as early as E14.5, homozygous mutant lenses show abnormal fiber cell differentiation
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cardiovascular system
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• at E11.5, mutant livers show abnormal trabecular structure with dilated sinusoids containing red cells, some of which are irregular and some apoptotic
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