mortality/aging
• no viable homozygotes are recovered from the progeny of heterozygous intercrosses
• however, homozygotes are recovered at normal Mendelian ratios with no detectable abnormalities up to E6.5
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embryo
• at E7.0, homozygotes show severe gastrulation defects, including a caudal bulge that corresponds to a significantly expanded primitive streak
• gastrulation defects are associated with increased expression of Nodal and can be partially suppressed by Nodal heterozygosity
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• at E7.0, homozygotes display little or no mesoderm migration circumferentially to the rostral side, with only limited movement observed anteriorly or extraembryonically
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• at E7.5, homozygotes display absence of mesoderm on the rostral side
• analysis of markers of nascent mesoderm indicates altered regional specification resulting in an expansion of axial mesendoderm at the expense of paraxial, lateral, and extraembryonic mesoderm
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• at E7.5, homozygotes exhibit limited anterior migration of axial mesendoderm
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• homozygotes display expansion of the axial mesoderm
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• homozygotes fail to specify paraxial mesoderm
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• at E7.5, homozygotes display abnormal primitive streak morphology, with nascent mesodermal cells retained within or near a greatly expanded primitive streak
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