Phenotypes Associated with This Genotype

Genotype
MGI:5695247

• Allelic Composition: Vps35^{Gt(RRK261)Byg}/Vps35⁺
• Genetic Background: B6.129P2-Vps35^{Gt(RRK261)Byg}

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

behavior/neurological

decreased vertical activity ( J:225806 )

• rearing frequency is decreased by 35.6% and 82.2% in 12- and 18- month old mice, respectively

decreased locomotor activity ( J:225806 )

• in the open field, total distance and velocity of 12- and 18-month old mice is reduced

• however, performance in the rotarod and gait tests is normal

homeostasis/metabolism

decreased dopamine level ( J:225806 )

• dopamine levels are reduced in the striatum and ventral midbrain at 6 month or older mutants

• ratios of 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine or 3,4-dihydroxyphenylacetic acid (HVA)/dopamine are much higher in 12 month old mutant striatum compared to controls

• however, 5-HT levels are normal

nervous system

abnormal dopaminergic neuron morphology ( J:225806 )

• TH+ neurons exhibit disturbed and decreased fibers/processes in substantia nigra pars compacta of aged mice

loss of dopaminergic neurons ( J:225806 )

• decrease in the number of TH+ neurons in aged (12 months) mice, with an approximate 20% loss of TH+ somas in the substantia nigra pars compacta

alpha-synuclein inclusion body ( J:225806 )

• mice show age-dependent accumulation of alpha-synuclein in in substantia nigra pars compacta-dopamine neurons

• both monomeric and oligomeric, or phosphorylated and unphosphorylated, species of alpha-synuclein are increased in mice older than 6 months, with an increase only in the ventral midbrain but not in the hippocampus

cellular

abnormal lysosome morphology ( J:225806 )

• Lamp1-positive late endosomes/early lysosomes appear enlarged in dopamine neurons

• Lamp2-positive vesicles appear smaller in size in dopamine neurons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 17		DOID:0060897	OMIM:614203	J:225806