Phenotypes Associated with This Genotype

Genotype
MGI:3702932

• Allelic Composition: Slc6a3^tm1(cre)Lrsn/Slc6a3⁺; Tfam^tm1Lrsn/Tfam^tm1Lrsn
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:119515 )

• mutants have to be terminated at ~45 weeks due to poor general condition

behavior/neurological

decreased exploration in new environment ( J:119515 )

• mice aged 14-15 weeks display decreased exploratory activity

tremors ( J:119515 )

• progressive Parkinsonian symptoms are observed, with tremor observed at 20 weeks of age

abnormal limb posture ( J:119515 )

• apparent limb rigidity is observed at 20 weeks of age

decreased locomotor activity ( J:119515 )

nervous system

abnormal dopaminergic neuron morphology ( J:119515 )

• 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

loss of dopaminergic neurons ( J:119515 )

• 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

neuronal intranuclear inclusions ( J:119515 )

muscle

muscle spasm ( J:119515 )

• twitching is observed at 20 weeks of age

homeostasis/metabolism

decreased dopamine level ( J:119515 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:119515