nervous system
• number of apoptotic cells in SNc increases in mutant brains at E14.5 and in neonates compared to heterozygotes
• in newborn mice, there are fewer neurons in the SNc and many of these cells have pyknotic neurons
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• at E12.5, a 45-50% reduction in tyrosine hydroxylase-positive (TH) neurons compared to wild-type is observed in the midbrain
• at E14.5, loss of dopaminergic neurons (DA) is more severe in the substantia nigra pars compacta (SNc) than in the ventral tegmental area in mutants; number of TH-positive neurons in GFP-positive population of the SNc (53.4%) compared to heterozygotes (88.2%)
• numbers of TH-positive cells in the GFP-positive population is reduced at E12.5 (43.7%) compared to heterozygous controls (64.8%)
• there is a reduction in cells expressing GFP and TH in the adult midbrain; midbrain dopaminergic neurons are absent rather than defective
• loss of DA neurons is progressive starting at beginning of terminal differentiation into adulthood
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• at E14.5, there are more GFP-positive tyrosine hydroxylase-negative (TH-) neurons in homozygotes than in heterozygous controls
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cellular
• number of apoptotic cells in SNc increases in mutant brains at E14.5 and in neonates compared to heterozygotes
• in newborn mice, there are fewer neurons in the SNc and many of these cells have pyknotic neurons
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