mortality/aging
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• although embryos are present at expected Mendelian ratios from E10.5 to E18.5, all pups die at P1 from respiratory failure
• no live mice are recovered at P10
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respiratory system
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• reduced ossification of the nasal bone at E17.5
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• lungs are hardly inflated at P1
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embryo
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• shortened body axis at P1
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craniofacial
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• severe craniofacial defects
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• severe hypoplasia and reduced ossification of many neural crest-derived bones at E17.5
• both the shape and size of most neural crest-derived bones including alisphenoid, premaxilla, palatal process of premaxilla, palatal process of maxilla and palatine are affected
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• reduced thickness of ossified calvaria at E17.5
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• frontal bones are hypoplastic and widely separated leaving a wide dorsal opening
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• reduced ossification of the nasal bone at E17.5
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• palatal process of palatine bone is missing at E17.5
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• Ki67 immunohistochemistry showed a significant decrease in mesenchymal cell proliferation in middle palatal shelves sections at E12.5, with a more pronounced reduction observed at E15.5
• no differences in apoptotic cell death or in E-caherin expression are observed in palatal shelves at E15.5
• primary palate development is normal
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• palatal shelves are elevated above the tongue to a horizontal position but completely fail to fuse at the midline throughout the anterior-posterior axis at E15.5 and E18.5
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• all fetuses (E15.5 and E18.5) and neonates show a secondary cleft palate defect
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skeleton
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• severe defects including a shortened axial skeleton at E17.5
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|
|
• severe hypoplasia and reduced ossification of many neural crest-derived bones at E17.5
• both the shape and size of most neural crest-derived bones including alisphenoid, premaxilla, palatal process of premaxilla, palatal process of maxilla and palatine are affected
|
|
|
• reduced thickness of ossified calvaria at E17.5
|
|
|
• frontal bones are hypoplastic and widely separated leaving a wide dorsal opening
|
|
|
• reduced ossification of the nasal bone at E17.5
|
|
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• palatal process of palatine bone is missing at E17.5
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• vertebral column is rather straight in the cervical and thoracic region, positioning the skull and vertebral column perpendicular to each other at E17.5; likely due to ectopic bone formation and fusion of vertebral bodies
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• fusion of vertebral bodies at E17.5
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• ectopic bone formation in the vertebral column at E17.5
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• reduced ossification of the nasal bone and many neural crest-derived bones at E17.5
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nervous system
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• hypoglossal nerve (XII cranial nerve) appears disorganized and shorter at E10.5; the roots of the hypoglossal nerve are not fully developed
• in contrast, dorsal root ganglion size is normal
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• oculomotor (III) appears deformed at E10.5
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• trochlear (IV) nerve appears deformed at E10.5
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growth/size/body
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• reduced ossification of the nasal bone at E17.5
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|
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• palatal process of palatine bone is missing at E17.5
|
|
|
• Ki67 immunohistochemistry showed a significant decrease in mesenchymal cell proliferation in middle palatal shelves sections at E12.5, with a more pronounced reduction observed at E15.5
• no differences in apoptotic cell death or in E-caherin expression are observed in palatal shelves at E15.5
• primary palate development is normal
|
|
|
• palatal shelves are elevated above the tongue to a horizontal position but completely fail to fuse at the midline throughout the anterior-posterior axis at E15.5 and E18.5
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|
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• all fetuses (E15.5 and E18.5) and neonates show a secondary cleft palate defect
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• smaller thoracic cavity at E17.5
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digestive/alimentary system
|
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• palatal process of palatine bone is missing at E17.5
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|
|
• Ki67 immunohistochemistry showed a significant decrease in mesenchymal cell proliferation in middle palatal shelves sections at E12.5, with a more pronounced reduction observed at E15.5
• no differences in apoptotic cell death or in E-caherin expression are observed in palatal shelves at E15.5
• primary palate development is normal
|
|
|
• palatal shelves are elevated above the tongue to a horizontal position but completely fail to fuse at the midline throughout the anterior-posterior axis at E15.5 and E18.5
|
|
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• all fetuses (E15.5 and E18.5) and neonates show a secondary cleft palate defect
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integument
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• severe subcutaneous edema at E15.5 and E17.5
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• thin dermal layer due to subcutaneous edema
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homeostasis/metabolism
cardiovascular system
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N |
• no alterations in smooth muscle actin staining in the aortic arches and normal septation and alignment of the aorta and pulmonary trunk at E18.5, indicating normal cardiac outflow tract development
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endocrine/exocrine glands
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N |
• normal thymus and adrenal gland (chromaffin cells) morphology at E18.5
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muscle
|
N |
• normal forelimb musculature at E17.5 and at P1
• normal diaphragm musculature at E15.5 and E17.5
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Analysis Tools