mortality/aging
• only a few mice escape neonatal lethality and exhibit a normal lifespan
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• >85% of mice die within the first few hours after birth
• however, no gross morphologic abnormalities are detected at E17.5 or at birth
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respiratory system
• moribund neonates show abnormal breathing and heavy gasping
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behavior/neurological
homeostasis/metabolism
nervous system
• mice exhibit impaired sprouting of secondary neurites in the diaphragm, as shown by lack of secondary branching
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• at E18.5, several callosal axons are misguided and form thick ectopic fascicles similar to Probst bundles, projecting ventrally instead of crossing the midline
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• co-staining for EdU+ and Tbr1+ revealed that a greater number of Tbr1+ cells are born at E12.5 in deep cortical layer VI
• however, a similar number of EdU+ cells is noted in the SVZ and superficial cortical layers relative to controls
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• at E18.5, the rostral part of the callosum is altered in shape
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• at E18.5, mice display aberrant cortical layering and a poorly defined preplate
• cortical layer VI is enlarged and the number of deep, early-born Tbr1+ neurons in layer VI is increased
• the number of superficial, late-born Satb2+ neurons in layers II-V is decreased
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• at E16.5, mice exhibit axon guiding or branching defects in phrenic nerve innervation
• at E10.5 and E12.5, abnormal innervation is detected in the trigeminal, hypoglossal, and spinal nerves
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• at E18.5, primary branches deriving from the phrenic nerve appear thinner than those in control mice
• as early as E16.5, the total length covered by secondary motor axons is markedly reduced while the number of secondary axons formed on the right ventral primary branch of the phrenic nerve is reduced by ~2-fold
• however, the overall distance covered by primary axons and the average length of individual secondary branches are normal
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• at E18.5, an overall thinning of the SVZ is observed, reflecting the early post-mitotic commitment of neural progenitors and reduction of their numbers
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• in culture, mutant primary hippocampal neurons exhibit significantly shorter neurites than wild-type neurons
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• at E18.5, the total number of neural progenitors (Pax6+) is decreased
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• at E18.5, the total number of post-mitotic cortical neurons (NeuN+) is decreased
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cellular
• mice exhibit impaired sprouting of secondary neurites in the diaphragm, as shown by lack of secondary branching
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• at E18.5, several callosal axons are misguided and form thick ectopic fascicles similar to Probst bundles, projecting ventrally instead of crossing the midline
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• co-staining for EdU+ and Tbr1+ revealed that a greater number of Tbr1+ cells are born at E12.5 in deep cortical layer VI
• however, a similar number of EdU+ cells is noted in the SVZ and superficial cortical layers relative to controls
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