Analysis Tools
mortality/aging
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• pups are born at the expected Mendelian ratio but die within a few hours of birth
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growth/size/body
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• mice fail to develop palatal shelves
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cleft palate
(
J:232855
)
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• embryos display fusion of medial edge epithelia leading to a cleft palate at E16.5
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omphalocele
(
J:232855
)
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• ~30% of E14.5 embryos exhibit omphalocele
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• at P0, the horizontal ribs are extremely short, resulting in a constricted thoracic cavity
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• at P0, pups are smaller than heterozygous and wild-type controls
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• at E14.5, embryos are smaller than normal
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limbs/digits/tail
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• at P0, forelimb phalangeal bones show reduced mineralization
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polydactyly
(
J:232855
)
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• ~30% of pups exhibit polydactyly
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• skeletal staining revealed preaxial polydactyly in hind limbs
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• at P0, metatarsal bones show reduced mineralization
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embryo
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• at E11.5, Shh staining is impaired and embryos show mild changes in the dorsoventral patterning of the neural tube
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• at E11.5, Shh staining is impaired and embryos show mild changes in the dorsoventral patterning of the neural tube
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• at E11.5, cilia number is reduced in the embryonic neural tube
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• at E11.5, Shh staining is absent in the floor plate while FoxA2 expression is reduced in the ventral floor plate
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craniofacial
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• at P0, the tympanic part of the temporal bone displays reduced mineralization
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• mice fail to develop palatal shelves
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cleft palate
(
J:232855
)
|
• embryos display fusion of medial edge epithelia leading to a cleft palate at E16.5
|
cardiovascular system
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• at P0, pups show severe malformation of the heart, including inversion of major blood vessels (truncus arteriosus) and ventricular septum defect
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• at E16.5
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skeleton
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• at P0, pups exhibit severe and fully penetrant skeletal defects
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• at P0, the tympanic part of the temporal bone displays reduced mineralization
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• at P0, forelimb phalangeal bones show reduced mineralization
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• at P0, metatarsal bones show reduced mineralization
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• at P0, pups exhibit sternebra fusion, ranging from fusion of all four sternebrae to only two
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short ribs
(
J:232855
)
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• at P0, the horizontal ribs are extremely short
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• at P0, the rib cage is shorter than normal
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• at P0, pups show an increase in cartilage at the expense of bone
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• at P0, pups show reduced mineralization in the tympanic bone and phalangeal and metatarsal bones
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nervous system
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• at E11.5, Shh staining is impaired and embryos show mild changes in the dorsoventral patterning of the neural tube
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• at E11.5, cilia number is reduced in the embryonic neural tube
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• at E11.5, Shh staining is absent in the floor plate while FoxA2 expression is reduced in the ventral floor plate
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• at P0, the pinwheel architecture of the ventricular surface is disrupted in neurogenic regions, suggesting abnormal neurogenesis due to reduced cilia number
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• at P0, an increase of aberrant mitotic cells is observed in brain ependymal epithelial cells, unlike in wild-type controls (~3% of metaphase nuclei versus 0%, respectively)
• among mitotic cells in ependymal epithelia, 10% show bipolar spindles and 45% show aberrant multipolar spindles, indicating supernumerary centrosomes and aneuploidy
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• at P0, less than 10% of ependymal epithelial cells are ciliated in the lining of lateral ventricles
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cellular
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• ~90% of serum-starved mouse embryonic fibroblasts (MEFs) derived from E12.5 embryos fail to develop cilia, unlike wild-type MEFs
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• only ~10% of MEFs derived from E12.5 embryos develop cilia upon serum starvation
• MEFs exhibit mislocalization of subdistal appendage (SDA) and transition zone components in the basal body, abnormal distribution of Rab11+ recycling endosomes, aberrant ciliary vesicle docking, and altered kinetics of microtubule array assembly
• TEM analysis of basal bodies revealed that, in most MEFs, the mother centriole (MC) lacks SDAs and fails to extend a ciliary axoneme
• less than 10% of MEFs exhibit ciliary vesicle docking; among the few MCs that are docked to a vesicle, none show an extended transition zone into the ciliary vesicle
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• at P0, less than 10% of ependymal epithelial cells are ciliated in the lining of lateral ventricles
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• at E11.5, cilia number is reduced in the embryonic neural tube
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• at P0, cilia number is reduced in the kidney collecting duct
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aneuploidy
(
J:232855
)
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• MEFs show an increase in aneuploidy (to 40%) relative to wild-type cells, confirming defects in G2/M phase
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polyploidy
(
J:232855
)
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• DNA content analysis revealed that MEFs fail to return to normal cell cycle within 24 h of nocodazole release and instead show accumulation of polyploid cells and appear to die, probably due to DNA damage, polyploidy and failure to segregate their centrioles
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• MEFs show a drastic reduction in the percentage of G1/S phase cells and a 28% increase in cells at the G2/M phase relative to wild-type MEFs
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• among mitotic cells in ependymal epithelia, 10% show bipolar spindles and 45% show aberrant multipolar spindles, indicating supernumerary centrosomes and aneuploidy
• among mitotic cells in serum-starved MEFs, 17% show bipolar spindles and ~80% show aberrant multipolar spindles; in addition, cells with supernumerary, unseparated centrosomes are often seen in the center of the cell, leading to complete failure of mitotic spindle formation
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• at P0, an increase of aberrant mitotic cells is observed in brain ependymal epithelial cells, unlike in wild-type controls (~3% of metaphase nuclei versus 0%, respectively)
• MEFs show a 28% increase in cells at the G2/M phase relative to wild-type MEFs
• ~2% of serum-starved MEFs are mitotic versus 0% in wild-type cells
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• most of the polyploid cells observed in MEFs exhibit lagging chromosomes, indicating chromosome breakage
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renal/urinary system
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• at P0, cilia number is reduced in the kidney collecting duct
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vision/eye
digestive/alimentary system
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• mice fail to develop palatal shelves
|
cleft palate
(
J:232855
)
|
• embryos display fusion of medial edge epithelia leading to a cleft palate at E16.5
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