Phenotypes Associated with This Genotype

Genotype
MGI:3846703

• Allelic Composition: Tg(Slc6a3-PARK2*Q311X)AXwy/0
• Genetic Background: FVB/NJ-Tg(Slc6a3-PARK2*Q311X)AXwy

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

behavior/neurological

impaired balance ( J:146833 )

• in beam tests, mice show more errors per step while traversing the beam compared with age; significant age effect is observed with performance in 3-6 month-old animals being comparable to controls but markedly impaired at 16-19 months

abnormal locomotor activation ( J:146833 )

• at 16-19 months, mice make significantly fewer hindlimb steps compared to controls

decreased vertical activity ( J:146833 )

• in cylinder tests, mice show decreased rearing compared to controls at 16-19 months

decreased locomotor activity ( J:146833 )

• at 3, 12, 16, and 21 months of age, mice display significantly progressive hypoactivity in open field tests

abnormal touch/ nociception ( J:146833 )

• in adhesive removal tests, at 16-19 months, mutants show significant deficits at 16-19 months

nervous system

abnormal substantia nigra morphology ( J:146833 )

• in the middle and caudal regions of the substantia nigra, significant numbers of alpha synuclein positive neurons are detected at 16 months, but not at 3 months; a chronic accumulation of proteinase K-resistant alpha-synuclein in midbrain neurons is observed in mutants

• dopaminergic neurons in the substantia nigra display oxidative protein damage at 16 months which is not as prevalent in wild-type mice

loss of dopaminergic neurons ( J:146833 )

• at 16 months, mice have a 40% reduction in tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta (SNc) coincident with a 30% reduction in total neuron number indicating a late-onset dopaminergic neuron loss

homeostasis/metabolism

decreased dopamine level ( J:146833 )

• in 19-21 month-old animals, dopamine (DA) levels are significantly reduced compared to controls which correlates with multiple hypokinetic motor deficits like open-field motor activity and vertical plane entries

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 2		DOID:0060368	OMIM:600116	J:146833