Analysis Tools
mortality/aging
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• perinatal lethality, with all mice dying within a few hours after birth
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growth/size/body
microcephaly
(
J:310617
)
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• newborns exhibit severe primary microcephaly, with a 48.5% reduction in cortical area and reduced neocortical thickness in the rostral, medial, and caudal aspects of the neocortex
• the reduction in head and brain weight is more pronounced than the reduction in body weight
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embryo
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• increase in the number of apoptotic cells in the developing brain and the rest of the body at E11.5, especially dorsal telencephalon cortical cells and hematopoietic progenitors in the embryonic liver
• increase in apoptotic cells in the developing neocortex at E14.5 but apoptotic cells are almost absent in the rest of the tissues at this time
• apoptotic cell death in both progenitor and neuroblast lineages in the E14.5 developing cortex
• however, no evidence of increased apoptotic cells is seen at E17.5
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nervous system
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• increase in the number of mitotic figures in the ventricular zone
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• 48.5% reduction in cortical area in newborns
• reduced cortical thickness at E14.5, E17.5, and birth
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• newborns show reduced neocortical thickness in the rostral, medial, and caudal aspects of the neocortex
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• cultured cortical neural progenitors exhibit a defect in self-renewal capacity
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digestive/alimentary system
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• intestinal mucosa is simplified and underdeveloped
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• intestinal mucosa is simplified and underdeveloped
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• stomach mucosa is simplified ad underdeveloped
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cellular
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• mouse embryo fibroblast (MEF) cultures are enriched in cells with only 1 centrosome and 1 centriole, suggesting both centrosome duplication and centriole assembly defects, as well as cells lacking a centrosome
• the 50% of MEFs with 2 centrosomes present defects such as centrosomal asymmetry in the maturation of centrosomes, typically affecting the daughter, newly generated centrosome, and not the mother centrosome
• SOX2+ apical progenitors in embryos show impaired maturation of centrosomes and asymmetric centrosomes
• centrioles of apical progenitor cells show aberrant axial structure, with lack or abnormal number of microtubule triplets, reduced centriolar diameter in some centriolar structures, and lack of a clear 9-fold symmetric conformation
• late G2 PH3+ cells also show centriole defects indicating that centriole defects are sustained during the rest of the cell cycle
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• MEFs exhibit increased nuclear volume and DNA content (4n and more than 4n)
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aneuploidy
(
J:310617
)
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• MEFs exhibit aneuploidy
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• MEFs do not show efficient centrosome duplication
• cultured cortical neural progenitors isolated from E14.5 neocortices exhibit centrosome duplication defects
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• MEFs exhibit increased duration of mitosis, with abundant monopolar spindles
• SOX2+ apical neural progenitors in embryos show frequent mitotic defects, including monopolar or acentrosomal mitotic spindles and apoptosis and maturation of centrosomes is impaired
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• about 50% of MEFs show a single gamma-tubulin spot from G1 to late G2, inducing monopolar spindles during mitosis
• SOX2+ apical progenitors in embryos show monopolar or acentrosomal mitotic spindles
• however, no differences in the orientation of the mitotic spindle in dividing cells of the apical progenitor layer is seen in embryos
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• increase in the number of apoptotic cells in the developing brain and the rest of the body at E11.5, especially dorsal telencephalon cortical cells and hematopoietic progenitors in the embryonic liver
• increase in apoptotic cells in the developing neocortex at E14.5 but apoptotic cells are almost absent in the rest of the tissues at this time
• apoptotic cell death in both progenitor and neuroblast lineages in the E14.5 developing cortex
• however, no evidence of increased apoptotic cells is seen at E17.5
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• E11.5 and E14.5 embryos show a reduced number of proliferating cells in several tissues
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• MEFs exhibit defective centriole dynamics, inducing chromosomal instability
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respiratory system
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• immature and underdeveloped lungs
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• lungs show small, immature alveolae
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vision/eye
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• retinal abnormalities
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