mortality/aging
• homozygotes die at midgestation before 10.5 dpc, possibly due to cardiac insufficiency
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cardiovascular system
• at 9.5 dpc, homozygotes display a hypoplastic, underdeveloped myocardium
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• ~20% of homozygotes show incomplete cardiac looping (tuba rectae)
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• ~40% of homozygous embryos show cardiac L-loops (situs inversus); in contrast, almost all wild-type embryos display a D-loop heart (situs solitas)
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• at 9.5 dpc, homozygotes display severe distention of the pericardium
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• at E9.5 dpc, extensive pericardial effusion leads to circulatory insufficiency
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embryo
• mutant show near absence of mature monocilia on nodal pit cells
• either no or extremely short cilia are observed
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• homozygotes show patterning defects in the neural tube, heart, brachial arches, and lower truncal mesoderm, resulting in severely underdeveloped posterior structures
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• at 9.5 dpc, embryonic turning remains incomplete in most cases, suggesting growth retardation
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• homozygotes display mesodermal and caudal dysgenesis
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• wild-type embryos contain motile monocilia on nodal pit cells and generate a leftward flow of extraembryonic fluid (nodal flow); in contrast, mutants lack motile monocilia and generate no nodal flow, suggesting impaired L-R determination
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• at 9.5 dpc, mutant embryos are smaller than wild-type embryos
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• at 9.5 dpc, mutant embryos exhibit swelling and degeneration of the neural tube
• at this stage, thinning of the neural tube wall is observed
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• at 9.5 dpc, staggering of the neural tube is noted at the incomplete turning region
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• at 9.5 dpc, homozygotes exhibit degeneration in the lower truncal part and abnormal somitegenesis (sirenomelia); somites appear highly disorganized
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growth/size/body
• at 9.5 dpc, mutant embryos are smaller than wild-type embryos
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nervous system
• at 9.5 dpc, mutant embryos exhibit swelling and degeneration of the neural tube
• at this stage, thinning of the neural tube wall is observed
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• at 9.5 dpc, staggering of the neural tube is noted at the incomplete turning region
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hydrocephaly
(
J:55332
)
• at 9.5 dpc, the neural tube dysmorphology resembles hydrocephalus
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homeostasis/metabolism
• at E9.5 dpc, extensive pericardial effusion leads to circulatory insufficiency
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cellular
• mutant show near absence of mature monocilia on nodal pit cells
• either no or extremely short cilia are observed
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muscle
• at 9.5 dpc, homozygotes display a hypoplastic, underdeveloped myocardium
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