Analysis Tools
mortality/aging
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• a single live-born pup was pale, runt, in obvious respiratory distress, and died within 15 minutes of birth
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• all delivered embryos (6%) are stillborn, with a single exception that died within 15 minutes of birth
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• homozygous embryos die steadily across a wide developmental span from ~E10.5 until birth
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growth/size/body
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• concentric hypertrophy of the cardiac ventricular wall at E19.5, suggesting increased vascular resistance
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• average gestational age-adjusted weight of live embryos is ~20% below that of wild-type controls
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• some of the embryos euthanized at E13.5 to E19.5 appear runted
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• embryos appear growth restricted
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embryo
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• placentas appear thinner and poorly developed at E19.5
• a striking number of microcalcifications are seen along the giant cell and spongiotrophoblastic layers, suggesting placental distress
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• poorly formed maternal vascular spaces at E19.5
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• collapse of the labyrinth reduces placenta thickness at E19.5
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immune system
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• a severely hypoplastic spleen is often seen at E19.5
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• significant B-cell lymphopenia at E13.5 and E19.5
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• a severely hypoplastic spleen is often seen at E19.5
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• marked underdevelopment of lymphoid tissues at E19.5
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cardiovascular system
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• concentric hypertrophy of the cardiac ventricular wall at E19.5, suggesting increased vascular resistance
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• the thin-walled capillary bed of fetal circulation is ill defined
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hemorrhage
(
J:229985
)
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• some of the embryos euthanized at E13.5 to E19.5 are hemorrhagic
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liver/biliary system
small liver
(
J:229985
)
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• embryonic livers are often small
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pale liver
(
J:229985
)
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• embryonic livers are often pale
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hematopoietic system
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• a severely hypoplastic spleen is often seen at E19.5
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• variable, multi-lineage hematopoietic deficiency at E13.5 and E19.5, with deficits in erythroid, granulocyte/macrophage, and lymphoid lineages, as shown by immunophenotyping of fetal liver cells and colony-forming assays
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• bone marrow hypoplasia at E19.5
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• significantly decreased number of hepatic megakaryocytes at E19.5
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• significant B-cell lymphopenia at E13.5 and E19.5
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• rarefaction of hepatic and bone marrow hematopoietic precursors across all lineages at E19.5, suggesting impaired hematopoiesis
• significantly reduced numbers of hematopoietic progenitor cells at E13.5 and E19.5, as shown by colony-forming assays
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• a severely hypoplastic spleen is often seen at E19.5
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• despite normal or even increased numbers of hematopoietic stem cells (HSCs), transplantation of mutant HSCs into lethally irradiated mice fails to reconstitute hematopoiesis
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respiratory system
small lung
(
J:229985
)
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• markedly small lungs at E19.5
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• marked lung hypoplasia at E19.5
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• broad, thick-walled terminal sacs lined by primarily bronchial-type cuboidal epithelium at E19.5
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• reduced branching of air spaces at E19.5
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nervous system
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• marked brain parenchymal hypercellularity at E19.5
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• cerebral hyperplasia at E19.5
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• reduced organization of layers I to VI of the diencephalic cortex with less distinct cortical layering at E19.5
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• no cerebellar lobations are present at the level of the choroid plexus in the IV ventricle at E19.5
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integument
endocrine/exocrine glands
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• a severely hypoplastic spleen is often seen at E19.5
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