Mouse Genome Informatics
hm1
    Pink1tm1Ncw/Pink1tm1Ncw
involves: 129S5/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• large lysosomes are observed in cultured cortical neurons
• cortical neuron cultures have a higher death rate (cytotoxicity) than controls after 20 days of plating
• the redox state of NADH in neuronal mitochondria is twice as more oxidized than controls
• incubating neurons in pyruvate restores redox state to control values
• neuronal stimulation causes a depolarization of internal mitochondria that is not observed in controls
• this depolarization results from overload of calcium concentrations in the mitochondria that is not observed in wild-type controls
• the basal mitochondrial ROS production in mouse neurons is two fold higher than in controls
• neuronal mitochondria membrane potential is largely maintained by the hydrolysis of ATP by complex V, rather than by respiration
• marked membrane depolarization can be triggered by drugs blocking complex V action

nervous system
• cultured cortical neurons have higher rates of apoptosis and contain large lysosomes
• neuron stimulation leads to a much higher internal calcium flux than controls
• stimulation also causes a depolarization of neuronal mitochondria that is not observed in controls
• this depolarization results from overload of calcium concentrations in the mitochondria that is not observed in wild-type controls
• cultured cortical neurons take up less glucose and altered mitochondrial redox states
• the basal cytosolic ROS production in mouse neurons is three fold higher than in controls
• glucose uptake by cultured neurons is only 41% of controls
• cortical neuron cultures have a higher death rate (cytotoxicity) than controls after 20 days of plating