Analysis Tools
mortality/aging
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• homozygous embryos die around E10.5; most embryos have been fully resorbed at E10.5
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embryo
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• increased apoptosis in regions containing migrating neural crest cells
• at E9.5, increased apoptosis in the forebrain, branchial arch and trunk regions of mutant embryos is observed
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• at E8.5, mutant neural crest cells (NCCs) are clustered next to the neuroectoderm/surface ectoderm border
• by E9.5, some NCCs fail to leave the region immediately adjacent to the laterally shifted neuroectoderm/surface ectoderm border, suggesting impaired emigration of nascent NCCs from the neural plate
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• by E9.5, branchial arches are often underdeveloped
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• mutant embryos display mild defects in signaling centers involved in D-V patterning of the developing neural tube
• however, A-P patterning of the brain is relatively normal
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• Background Sensitivity: at E9.5, embryos display a failure of the turning process on 129 x B6 background; on 129 x CD-1 background, most mutant embryos turn by E9.5 but display twisted body axes with multiple kinks
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• expansion of the neuroectoderm and reduction of the surface ectoderm results in a lateral shift of the cranial neuroectoderm/surface ectoderm border
• the ratio of cranial surface ectoderm to neuroectoderm is reduced by 2-fold
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• there is a paucity of cranial mesenchyme and no surface ectoderm covering the forebrain region
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• Background Sensitivity: at ~E8.5-8.75, neural folds appear larger and more rounded on 129 x B6 background; not all mutants show a dramatic rounding of the neural folds on 129 x CD-1 background
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• at E8.5, the neuroectoderm is expanded and folded laterally towards the surface ectoderm, leading to an apparent lateral shift of the cranial neuroectoderm/surface ectoderm junction
• at E8.5, the transition from the columnar epithelial morphology of the neuroectoderm to the cuboidal epithelium of the surface ectoderm is not as distinct and appears to be more gradual
• the ratio of cranial surface ectoderm to neuroectoderm is reduced by 2-fold in mutants
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• mutant s display an increase in the contour of the neuroectoderm
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• by E9.5, all mutant embryos exhibit a failure of cranial neural tube closure
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spina bifida
(
J:106405
)
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• at E9.5, a single "escaper" on 129 x CD-1 background showed open regions in trunk neural tube along with areas of open cranial neural tube
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• notochords display multiple kinks indicating twisted or improper extension of the body axis
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• at E8.5, the prechordal plate region is not as rostrally extended (i.e. truncated) and lacks the typical hook-shaped morphology
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nervous system
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• at E8.5, the neuroectoderm is expanded and folded laterally towards the surface ectoderm, leading to an apparent lateral shift of the cranial neuroectoderm/surface ectoderm junction
• at E8.5, the transition from the columnar epithelial morphology of the neuroectoderm to the cuboidal epithelium of the surface ectoderm is not as distinct and appears to be more gradual
• the ratio of cranial surface ectoderm to neuroectoderm is reduced by 2-fold in mutants
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• mutant s display an increase in the contour of the neuroectoderm
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• by E9.5, all mutant embryos exhibit a failure of cranial neural tube closure
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spina bifida
(
J:106405
)
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• at E9.5, a single "escaper" on 129 x CD-1 background showed open regions in trunk neural tube along with areas of open cranial neural tube
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• on CD-1 X 129 background, in some embryos, forebrain develops as two separate hollow tubes instead of forming a single vesicle
• there is a paucity of cranial mesenchyme and no surface ectoderm covering the forebrain region
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• a slight but significant decrease in proliferation in the neuroectoderm is detected at E8.5
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cardiovascular system
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• at E8.5, all mutant embryos display severely defective heart development
• Background Sensitivity: cardiac defects are slightly more severe on the 129 x B6 background
• mutant hearts display an indistinct outflow tract/aortic region and an indistinct atriosinus region
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• mutant hearts display abnormal patterns of looping and septation resulting in a single ventricular chamber abutted by two lateral atrium-like structures
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• at E8.5, mutant embryos either show failure of fusion of the left and right heart primordia or lack any heart primordium
• as development progresses, mutant hearts form single heart tube, but are much smaller than age-matched wild-type hearts
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• at E8.5, in some mutants the two heart fields fail to fuse properly
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• at E9.5, septation between the future right and left ventricles is not observed
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digestive/alimentary system
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• gut epithelium appears less developed in mutants compared to wild-type
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• foregut lacks eosin-positive acellular debris normally present within wild-type lumen
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• differentiation of hindgut endoderm is delayed in mutants
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hearing/vestibular/ear
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• Background Sensitivity: on a 129 x B6 background, at E9.5, the otic pit has not formed; on 129 x CD-1 background, at E9.5, rudimentary otic structures are often seen
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vision/eye
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• Background Sensitivity: on 129 x B6 background, at E9.5, the optic eminence has not formed; on 129 x CD-1 background, at E9.5, rudimentary optic structures are often seen
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craniofacial
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• at ~E8.5-8.75, optic invaginations are not observed on 129 x B6 background
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• Background Sensitivity: on a 129 x B6 background, at E9.5, the otic pit has not formed; on 129 x CD-1 background, at E9.5, rudimentary otic structures are often seen
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• by E9.5, branchial arches are often underdeveloped
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cellular
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• increased apoptosis in regions containing migrating neural crest cells
• at E9.5, increased apoptosis in the forebrain, branchial arch and trunk regions of mutant embryos is observed
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• at E8.5, mutant neural crest cells (NCCs) are clustered next to the neuroectoderm/surface ectoderm border
• by E9.5, some NCCs fail to leave the region immediately adjacent to the laterally shifted neuroectoderm/surface ectoderm border, suggesting impaired emigration of nascent NCCs from the neural plate
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growth/size/body
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• there is a paucity of cranial mesenchyme and no surface ectoderm covering the forebrain region
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