mortality/aging
• fewer than expected mutants are found at 4 weeks of age (8% rather than 25%)
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embryo
• at E7.5 expression of Hex, a marker of anterior definitive endoderm, is often undetectable; however Hex expression in visceral endoderm is normal
• at E8.25 expression of Shh marking ventral midline structures and gut endoderm is greatly reduced or absent
• these changes in expression indicate defects in axial mesendoderm and definitive endoderm development with a nearly complete loss of definitive endoderm in severely affected embryos
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• defects in axial mesendoderm development
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• severely affected embryos show anterior truncations
• less affected embryos display anterior restricted phenotypes
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• at E7.5 expression of Hex, a marker of anterior definitive endoderm, is often undetectable
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• in severely affected embryos the anterior somites are fused across the midline indicating the absence of the notochord
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• at E7.75 an intact prechordal plate fails to form
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• in severely affected embryos the anterior somites are fused across the midline indicating the absence of the notochord
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nervous system
• at E8.25 - E9.5, about 56% display a broad spectrum of phenotypes with characteristic features of holoprosencephaly
• at E11.5 severely affected embryos have a single prosencephalic vesicle
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• at E9.0 - E11.5 less severely affected embryos have variable forebrain reductions including truncation of the rostral forebrain
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• at E9.0 - E11.5 less severely affected embryos have variable midbrain reductions
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vision/eye