mortality/aging
• homozygous mice always die within 2-24 hours of birth
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behavior/neurological
• pups do not suckle
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• neonatal pups are relatively inactive
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nervous system
• homozygous neonatal mice exhibit an overall higher number of TUNEL stained cells in the developing brain than control littermates, predominantly in regions that normally express alpha-7 nAChRs
• increased TUNEL labeling is also visible in the ventral posterior medial nucleus and in the habenula
• interestingly, the hippocampus and olfactory bulb of homozygous mice, which exhibit high levels of a7 mRNA and 125I-alpha-BTX binding site expression in normal animals, showed lower levels of TUNEL cell labeling relative to the somatosensory cortex, yet higher than in littermate controls
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• a significant reduction in 125I-alpha-BTX binding was observed throughout the brain in neonatal mice compared to controls; levels are reduced by as much as 65-75% in the somatosensory cortex, hippocampus, and olfactory bulb of the brains of homozygous neonatal mice
• gross morphology of the brain is similar to controls
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• at P0, in the somatosensory cortex of homozygous mice, apoptotic cell death was observed throughout layers 6 and 5 and was rarely seen in the cortical plate
• in addition, no clear differentiation between layers 6 and 5 is seen; instead, there were small densely packed cells throughout this region
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• in homozygous mice, the currents evoked by 500 mM nicotine were inhibited by 5 nM MLA but showed little desensitization; the current amplitude was relatively small compared with controls
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cellular
• homozygous neonatal mice exhibit an overall higher number of TUNEL stained cells in the developing brain than control littermates, predominantly in regions that normally express alpha-7 nAChRs
• increased TUNEL labeling is also visible in the ventral posterior medial nucleus and in the habenula
• interestingly, the hippocampus and olfactory bulb of homozygous mice, which exhibit high levels of a7 mRNA and 125I-alpha-BTX binding site expression in normal animals, showed lower levels of TUNEL cell labeling relative to the somatosensory cortex, yet higher than in littermate controls
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