mortality/aging
• homozygotes die at ~E11.5
• by E12.5, homozygotes appear highly necrotic and pale (presumably due to anemia) and show no signs of life
|
nervous system
• at E9.5, homozygotes exhibit a wavy neuroepithelium and an aberrant ectodermal surface
• by E11.5, the neuroepithelium is thin and lacks architectural complexity
|
• at E9.5, homozygotes display an abnormal prosencephalon
|
• at E9.5, homozygotes display an abnormal roof plate in the myelencephalon
|
• at E11.5, homozygotes display hypoplastic telencephalic structures
|
• by E11.5, cranial ganglia are generally reduced, with a mitotic rate of less than 25% of wild-type
|
• by E11.5, homozygotes display lack of organization and a reduction of neurite outgrowths in the trigeminal ganglia
|
• by E11.5, homozygotes display a reduction of neurite outgrowths in the dorsal root ganglia
|
respiratory system
• at E10.5, the mutant lung epithelium fails to undergo proper branching; as a result, mutant lungs appear as simple tube-like structures
• however, no morphologic abnormalities are noted in the mesenchymal component
|
• at E10.5, mutant lungs fail to display branching morphogenesis
|
digestive/alimentary system
• at E10.5-E11.5, homozygotes display abnormal growth and/or disorganization of the gut epithelium
|
• at E11.5, homozygotes lack an identifiable large intestine
|
absent stomach
(
J:3432
)
• at E11.5, homozygotes lack an identifiable stomach
|
embryo
• at E9.5, homozygotes display hypoplasia of the mandibular arch, the first postoral arch in the branchial arch series
|
• as early as E9.5, homozygotes display hypoplasia of several organ systems, particularly those of epithelial origin such as the lung and gut
|
• homozygotes become growth arrested at ~E11.5
|
• starting at E10.5, homozygotes exhibit progressive growth retardation
• by E11.5, homozygotes are ~40% the size of wild-type embryos
|
• at E9.5, homozygotes appear thinner in transverse dimension relative to wild-type embryos
|
• at E11.5, homozygotes exhibit a hypoplastic genital ridge with an irregular, hobnail-like coelomic epithelium
• both the stromal and germ cell components of the genital ridge are severly hypoplastic (~1/10 of wild-type size)
|
• at E9.5, some (but not all) homozygotes exhibit a slight delay in the initial formation of the mesonephric tubules
• by E11.5, some tubules appear normal while others fail to form or undergo premature degeneration
|
• at E9.5, some (but not all) homozygotes exhibit a slight delay in the initial formation of the mesonephric duct
|
• at E9.5, homozygotes exhibit a wavy neuroepithelium and an aberrant ectodermal surface
• by E11.5, the neuroepithelium is thin and lacks architectural complexity
|
cardiovascular system
• at E11.5, the mutant dorsal aorta is dilated
|
• at E11.5, homozygotes display a thinned myocardium
|
hemorrhage
(
J:3432
)
• at E11.5, homozygotes are fragile and bleed easily, despite the presence of a beating heart
|
craniofacial
• at E9.5, homozygotes display hypoplasia of the mandibular arch, the first postoral arch in the branchial arch series
|
growth/size/body
• starting at E10.5, homozygotes exhibit progressive growth retardation
• by E11.5, homozygotes are ~40% the size of wild-type embryos
|
• at E9.5, homozygotes appear thinner in transverse dimension relative to wild-type embryos
|
hematopoietic system
renal/urinary system
• the mesenchyme surrounding the mesonephric tubules is hypoplastic
|
muscle
• at E11.5, homozygotes display a thinned myocardium
|