mortality/aging
nervous system
• several embryos show a rudimentary vomeronasal organ
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• mice exhibit defective neuronal patterning at the hind limb level of the neural tube
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• at E10.5
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exencephaly
(
J:255606
)
• 30% of embryos show massive exencephaly with distinct abnormalities in head shape at E12.5
|
• 67% of embryos show optic nerve hypoplasia
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limbs/digits/tail
• at E13.5
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embryo
• mice exhibit defective neuronal patterning at the hind limb level of the neural tube
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• at E10.5
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craniofacial
• multiple gross morphological defects in craniofacial regions evident at E12.5
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• altered rostrum morphology at E12.5
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• abnormal basisphenoid bone morphology with delayed development of chondrogenesis as well as delayed ossification at E15.5
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• delayed ossification of basisphenoid bone in all embryos at E15.5
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• Meckels cartilage is shorter at E16.5
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• shape defects in nasal septum cartilage with enlarged nasal septum or defects in vomeronasal cartilage formation
• cartilages surrounding the vomeronasal organ show altered shape and are fused in the midline or missing
• delayed chondrogenesis in basisphenoid cartilage at E15.5
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• smaller frontal bone at E15.5
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• smaller parietal bones at E15.5
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• mandibular bone ossification center is significantly shorter at E15.5
• mandibular bones are deformed at E16.5
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• mandible is shortened in all embryos at E16.5
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• maxilla is abnormal or reduced in size in all embryos at E16.5
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• palatal process of the maxillary bone is reduced at E16.5
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• no premaxillary ossification center is visible at E15.5
• premaxilla is abnormal or reduced in size in all embryos at E16.5, with premaxilla fusing across the ventral midline in 3 of 6 embryos
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• smaller maxillary bone at E15.5
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• palatine bones are reduced at E16.5
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• 5 of 6 embryos show a reduced zygomatic bone at E16.5
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• expansion of the facial midline at E12.5, indicating disruption of Shh signaling
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• 4 of 6 embryos show total absence of the nasal bone at E16.5
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• 2 of 6 embryos show a smaller nasal bone at E16.5
|
• increased palatal mesenchymal proliferation at E13.5 and E14.5 leading to early overgrowth of palatal shelves followed by defects in their horizontalization
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• most mice develop only indistinct medial outgrowth of palatal processes at E12.5, indicating delayed growth of palatal shelves
• anterior palatal shelves are misshapen or enlarged (thicker) and improperly oriented under the tongue at E14.5 and E15.5
• expression of epithelial stemness marker SOX2 is altered in the palatal shelves; SOX2 is NOT downregulated in the lingual side and the tip of the shelves during horizontalization
• differences in mesenchymal SOX9 expression indicate enhanced neural crest migration
|
• onset of ossification is delayed in the palatal shelves at E15.5
• however, palatal shelves are ossified by E16.5
|
• delay in palatal shelves growth at E12.5 and E13.5
• secondary palate remains open during normal fusion stages between E14.5 and E15.5 as well as at E16
|
• cleft lip and palate at E13.5-E15.5
• 14% of embryos show extensive cleft lip
|
• in most cases (4 of 5), cleft lip is one-sided and extends into the nasal cavity
|
• increased expression of Shh and its downstream target Gli1 in the palatal ridges at E14.5
|
cleft palate
(
J:255606
)
• cleft lip and palate at E13.5-E15.5
|
• clefting of the secondary palate due to altered growth of palatal shelves
|
• anterior palatal shelves are improperly oriented under the tongue at E14.5
• at E15.5, palatal shelves were still vertically oriented in one case or they grew horizontally but were not touching each other in the anterior part due to bilateral asymmetry
|
• tongue is smaller and misshapen at E12.5 and E13.5
|
• tongue is located above palatal shelves during palatal closure
|
• tongue is smaller at E13.5
|
• shape defects in nasal septum cartilage with enlarged nasal septum at E15.5
|
• altered shape of vomeronasal cartilage at E15.5
|
• several embryos show a rudimentary vomeronasal organ
|
• enlarged nasal septum at E15.5
|
• nasal septum is slightly wider at E15.5
|
• snout is wider and shorter at E15.5
|
broad snout
(
J:255606
)
• broader snout at E15.5
|
short snout
(
J:255606
)
• shorter snout at E14.5 and E15.5
|
• 30% of embryos show massive exencephaly with distinct abnormalities in head shape at E12.5
|
vision/eye
• 67% of embryos show optic nerve hypoplasia
|
• in some cases, eye development is arrested with only a small pigmented layer or lens pit that appears to result from increased apoptosis and downregulation of the SOX2 progenitor marker at E13.5
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• 67% of embryos show reduced or absent eyes at E12.5-E15.5
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anophthalmia
(
J:255606
)
• 67% of embryos show reduced or absent eyes at E12.5-E15.5
|
growth/size/body
• expansion of the facial midline at E12.5, indicating disruption of Shh signaling
|
• palatal process of the maxillary bone is reduced at E16.5
|
• 4 of 6 embryos show total absence of the nasal bone at E16.5
|
• 2 of 6 embryos show a smaller nasal bone at E16.5
|
• increased palatal mesenchymal proliferation at E13.5 and E14.5 leading to early overgrowth of palatal shelves followed by defects in their horizontalization
|
• most mice develop only indistinct medial outgrowth of palatal processes at E12.5, indicating delayed growth of palatal shelves
• anterior palatal shelves are misshapen or enlarged (thicker) and improperly oriented under the tongue at E14.5 and E15.5
• expression of epithelial stemness marker SOX2 is altered in the palatal shelves; SOX2 is NOT downregulated in the lingual side and the tip of the shelves during horizontalization
• differences in mesenchymal SOX9 expression indicate enhanced neural crest migration
|
• onset of ossification is delayed in the palatal shelves at E15.5
• however, palatal shelves are ossified by E16.5
|
• delay in palatal shelves growth at E12.5 and E13.5
• secondary palate remains open during normal fusion stages between E14.5 and E15.5 as well as at E16
|
• cleft lip and palate at E13.5-E15.5
• 14% of embryos show extensive cleft lip
|
• in most cases (4 of 5), cleft lip is one-sided and extends into the nasal cavity
|
• increased expression of Shh and its downstream target Gli1 in the palatal ridges at E14.5
|
cleft palate
(
J:255606
)
• cleft lip and palate at E13.5-E15.5
|
• clefting of the secondary palate due to altered growth of palatal shelves
|
• anterior palatal shelves are improperly oriented under the tongue at E14.5
• at E15.5, palatal shelves were still vertically oriented in one case or they grew horizontally but were not touching each other in the anterior part due to bilateral asymmetry
|
• tongue is smaller and misshapen at E12.5 and E13.5
|
• tongue is located above palatal shelves during palatal closure
|
• tongue is smaller at E13.5
|
• shape defects in nasal septum cartilage with enlarged nasal septum at E15.5
|
• altered shape of vomeronasal cartilage at E15.5
|
• several embryos show a rudimentary vomeronasal organ
|
• enlarged nasal septum at E15.5
|
• nasal septum is slightly wider at E15.5
|
• snout is wider and shorter at E15.5
|
broad snout
(
J:255606
)
• broader snout at E15.5
|
short snout
(
J:255606
)
• shorter snout at E14.5 and E15.5
|
• 30% of embryos show massive exencephaly with distinct abnormalities in head shape at E12.5
|
skeleton
• altered rostrum morphology at E12.5
|
• abnormal basisphenoid bone morphology with delayed development of chondrogenesis as well as delayed ossification at E15.5
|
• delayed ossification of basisphenoid bone in all embryos at E15.5
|
• Meckels cartilage is shorter at E16.5
|
• shape defects in nasal septum cartilage with enlarged nasal septum or defects in vomeronasal cartilage formation
• cartilages surrounding the vomeronasal organ show altered shape and are fused in the midline or missing
• delayed chondrogenesis in basisphenoid cartilage at E15.5
|
• smaller frontal bone at E15.5
|
• smaller parietal bones at E15.5
|
• mandibular bone ossification center is significantly shorter at E15.5
• mandibular bones are deformed at E16.5
|
• mandible is shortened in all embryos at E16.5
|
• maxilla is abnormal or reduced in size in all embryos at E16.5
|
• palatal process of the maxillary bone is reduced at E16.5
|
• no premaxillary ossification center is visible at E15.5
• premaxilla is abnormal or reduced in size in all embryos at E16.5, with premaxilla fusing across the ventral midline in 3 of 6 embryos
|
• smaller maxillary bone at E15.5
|
• 4 of 6 embryos show total absence of the nasal bone at E16.5
|
• 2 of 6 embryos show a smaller nasal bone at E16.5
|
• palatine bones are reduced at E16.5
|
• 5 of 6 embryos show a reduced zygomatic bone at E16.5
|
• shape defects in nasal septum cartilage with enlarged nasal septum at E15.5
|
• altered shape of vomeronasal cartilage at E15.5
|
• ossification of the frontal, parietal, and interparietal bones is reduced at E16.5; one of 6 embryos showed no signs of interparietal ossification
|
• onset of ossification is delayed in the palatal shelves at E15.5
• however, palatal shelves are ossified by E16.5
|
• onset of ossification is delayed in several facial membranous bones; at E15.5, the ossification center of the mandibular bone is significantly shorter while the premaxillary ossification center is not detectable
|
respiratory system
• 4 of 6 embryos show total absence of the nasal bone at E16.5
|
• 2 of 6 embryos show a smaller nasal bone at E16.5
|
• shape defects in nasal septum cartilage with enlarged nasal septum at E15.5
|
• altered shape of vomeronasal cartilage at E15.5
|
• several embryos show a rudimentary vomeronasal organ
|
• enlarged nasal septum at E15.5
|
• nasal septum is slightly wider at E15.5
|
digestive/alimentary system
• palatal process of the maxillary bone is reduced at E16.5
|
• increased palatal mesenchymal proliferation at E13.5 and E14.5 leading to early overgrowth of palatal shelves followed by defects in their horizontalization
|
• most mice develop only indistinct medial outgrowth of palatal processes at E12.5, indicating delayed growth of palatal shelves
• anterior palatal shelves are misshapen or enlarged (thicker) and improperly oriented under the tongue at E14.5 and E15.5
• expression of epithelial stemness marker SOX2 is altered in the palatal shelves; SOX2 is NOT downregulated in the lingual side and the tip of the shelves during horizontalization
• differences in mesenchymal SOX9 expression indicate enhanced neural crest migration
|
• onset of ossification is delayed in the palatal shelves at E15.5
• however, palatal shelves are ossified by E16.5
|
• delay in palatal shelves growth at E12.5 and E13.5
• secondary palate remains open during normal fusion stages between E14.5 and E15.5 as well as at E16
|
• increased expression of Shh and its downstream target Gli1 in the palatal ridges at E14.5
|
cleft palate
(
J:255606
)
• cleft lip and palate at E13.5-E15.5
|
• clefting of the secondary palate due to altered growth of palatal shelves
|
• anterior palatal shelves are improperly oriented under the tongue at E14.5
• at E15.5, palatal shelves were still vertically oriented in one case or they grew horizontally but were not touching each other in the anterior part due to bilateral asymmetry
|
• tongue is smaller and misshapen at E12.5 and E13.5
|
• tongue is located above palatal shelves during palatal closure
|
• tongue is smaller at E13.5
|
cellular
• altered length and morphology of primary cilia in the anterior, middle, and posterior areas of palatal shelf surfaces at E12.5, with numerous abnormal elongated, curly or very short cilia
• high variability in cilia length, esp. in the anterior or middle areas of the palate; occasionally, enlargements or bulges are found on the most distal cilia tip
• primary cilia labeled by alpha-acetylated tubulin appear to be elongated and have altered shape in both ventral and dorsal parts of the anterior palatal shelves
• altered primary cilia morphology is accompanied by upregulated expression of IFT88 and Shh signaling
|