Mouse Genome Informatics
cn
    Slc6a3tm1(cre)Lrsn/Slc6a3+
Tfamtm1Lrsn/Tfamtm1Lrsn

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• mutants have to be terminated at ~45 weeks due to poor general condition

behavior/neurological
• mice aged 14-15 weeks display decreased exploratory activity
• progressive Parkinsonian symptoms are observed, with tremor observed at 20 weeks of age
• apparent limb rigidity is observed at 20 weeks of age

nervous system
• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks
• majority of neurons contain small cytoplasmic aggregates, detected at 6 weeks through 43 weeks
• inclusions are present in most dopaminergic midbrain neurons and the mean size increased as the neurodegeneration progressed
• large, partially electron-dense bodies located in dendritic structures close to neuronal somata are observed at 11 weeks; some of these bodies have an amorphous content with a diffuse lining, while others display tubular formations and have distinct double layer membranes which are ultrastructurally typical of mitochondrial membranes
• dopaminergic (DA) neuron loss is observed in the dorsolateral striatum at 12 weeks of age, progressing to involve most of the dorsal and ventral striatum with age
• tyrosine hydroxylase-expressing midbrain neurons show a slow progressive cell loss, which is more marked and starts sooner in the substantia nigra compared to the ventral tegmental area

muscle
• twitching is observed at 20 weeks of age

homeostasis/metabolism
• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease, Mitochondrial 556500 J:119515