mortality/aging
• mice die neonatally due to an inability to start breathing
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respiratory system
• none of the newborn mice start to breathe and alveoli of newborns are not expanded with air
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nervous system
• cortical neurons form functional synapses in vitro, but their spontaneous activity is abnormal, with calcium oscillations being of an abnormally high amplitude and low frequency and they are highly synchronized
• however, no anatomical defects are seen in the brain at E19
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• cortical neurons are defective for the developmental switch in GABAergic neurotransmission
• cortical neuron cultures treated with the GABA(A)R inhibitor gabazine show a reduction in the amplitude and an increase in the frequency of calcium oscillations, the opposite of wild-type cultures which show increased amplitude and decreased frequency of calcium oscillations
• cortical neuron cultures and brain slice cultures treated with the GABA(A)R agonist muscimol show increased intracellular calcium compared to wild-type cultures in which few neurons respond to muscimol
• more neurons from spinal cord slices respond to a mix of GABA and glycine with elevated intracellular calcium than in wild-type slices
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