Phenotypes Associated with This Genotype

Genotype
MGI:7378801

• Allelic Composition: Vps35^tm1.1Mjff/Vps35^tm1.1Mjff
• Genetic Background: B6.Cg-Vps35^tm1.1Mjff

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

cellular

abnormal mitochondrial shape ( J:303283 )

• mitochondria from neurons from the substanta nigra pars compacta of 14-month-old mice are shorter, rounder, smaller and less dense than controls

abnormal mitochondrial physiology ( J:303283 )

• basal OCR (oxygen consumption rate), maximal OCR and spare OCR are reduced in 15-month-old mice

behavior/neurological

behavior/neurological phenotype ( J:303283 )

N • no differences in rotarod test or grip strength

impaired coordination ( J:303283 )

• decrease in latency to fall in rotarod test following MTPT (neurotoxin) treatment in 3-month-old mice

• increased time to cross 9 mm beam following MTPT treatment in 3-month-old mice

decreased locomotor activity ( J:303283 )

• reduction in mean speed and travel distance in open field test is observed in 14-month-old mice as compared to wild-type

• increase in time to cross beam in 14-month-old mice as compared to controls

hematopoietic system

microgliosis ( J:303283 )

• increased microgliosis in substanta nigra pars compacta (but not striatum) of MPTP-treated 3-month-old mice as compared to MPTP-treated controls

homeostasis/metabolism

abnormal nervous system dopamine level ( J:274797 )

• Increased dopamine release in dorsolateral striatal slices as measured by fast scan cyclic voltammetry

• Decay time of dopamine transient is slower in dorsolateral striatal slices

• Increased dopamine turnover as measured by ration of dopamine metabolites to dopamine

• In response to a D2 agonist, quinpirole, dorsolateral striatal slices exhibit a more rapid inhibition of dopamine release

nervous system

microgliosis ( J:303283 )

• increased microgliosis in substanta nigra pars compacta (but not striatum) of MPTP-treated 3-month-old mice as compared to MPTP-treated controls

abnormal nervous system dopamine level ( J:274797 )

• Increased dopamine release in dorsolateral striatal slices as measured by fast scan cyclic voltammetry

• Decay time of dopamine transient is slower in dorsolateral striatal slices

• Increased dopamine turnover as measured by ration of dopamine metabolites to dopamine

• In response to a D2 agonist, quinpirole, dorsolateral striatal slices exhibit a more rapid inhibition of dopamine release

astrocytosis ( J:303283 )

• astrogliosis observed in 15-16-month-old mice in the substanta nigra pars compacta, but not in the striatum

abnormal dopaminergic neuron morphology ( J:303283 )

• neurons contain increased numbers of lysosomes with dense bodies or other inclusions in substanta nigra pars compacta of 14-month-old mice

decreased dopaminergic neuron number ( J:303283 )

• decreased levels of TH-positive dopaminergic neurons (12%) in substanta nigra pars compacta of 15-16-month-old mice

• decreased levels of TH-positive dopaminergic nerve terminals (25%) in striatum of 15-16-month-old mice

• decreased TH-positive neurons and TH-positive striatal fibers in MPTP-treated 3-month-old mice as compared to MPTP-treated controls (36% vs. 51%)

abnormal axon morphology ( J:303283 )

• dystrophic myelinated axons contain autophagic vacuoles in substanta nigra pars compacta of 14-month-old mice

alpha-synuclein inclusion body ( J:303283 )

• accumulation and aggregation of alpha-synuclein is observed in substanta nigra pars compacta of 15-16-month-old mice, no tau pathology is observed

neurodegeneration ( J:303283 )

immune system

microgliosis ( J:303283 )

• increased microgliosis in substanta nigra pars compacta (but not striatum) of MPTP-treated 3-month-old mice as compared to MPTP-treated controls

pigmentation

lipofuscinosis ( J:303283 )

• increased numbers of lipofuscins in substanta nigra pars compacta of 14-month-old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:303283