Phenotypes associated with this allele

• Allele Symbol: Slc18a2^tm2Kmo
• Allele Name: targeted mutation 2, Katrin A Mooslehner
• Allele ID: MGI:2182936
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc18a2^tm2Kmo/Slc18a2^tm2Kmo	involves: 129P2/OlaHsd * C57BL/6	MGI:3758030

Genotype
MGI:3758030

hm1

• Allelic Composition: Slc18a2^tm2Kmo/Slc18a2^tm2Kmo
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

growth/size/body

decreased body weight ( J:70606 )

• mice weigh 29.2 grams compared to 35.1 grams for wild-type

behavior/neurological

abnormal emotion/affect behavior ( J:150414 )

decreased coping response ( J:150414 )

• immobility times are higher in a forced swim rest and tail suspension test compared to age matched controls at 12 - 15 months of age

increased anxiety-related response ( J:150414 )

• spend more time in the closed arm of an elevated plus maze at 4 - 6 months of age but not at 12 - 15 months of age

abnormal response to novelty ( J:150414 )

abnormal response to new environment ( J:70606 )

• when tested for response to novelty, homozygotes show decreased number of rearings in novel compartment and fewer visits to novel compartment, compared to wild-type

abnormal response to novel odor ( J:150414 )

• unable to discriminate between wooden block scented with either home cage bedding or bedding from the cage of a foreign mouse of the same sex at 5, 6, and 12 months of age

• only at 12 months of age is the total investigatory time reduced relative to age matched wild-type controls

abnormal motor capabilities/coordination/movement ( J:150414 )

impaired coordination ( J:70606 )

• in beam walking tests, mutants take longer and have more slips during beam crossing

decreased locomotor activity ( J:123245 , J:150414 )

• 40% decrease in locomotor activity is observed at 2, 6, and 12 months; at 18 months of age, activity is reduced by 60% compared to wild-type (J:123245)

• activity levels are substantially restored by administration of L-DOPA (J:123245)

• only at 12 months of age, but not at 4, 5, or 6 months of age, is the total investigatory time reduced relative to age matched wild-type controls in an odor discrimination assay (J:150414)

stereotypic behavior ( J:70606 )

• mice display enhanced stereotypic behaviors in response to amphetamine injection

abnormal circadian behavior ( J:150414 )

• circadian activity is significantly lower at 4 - 6 months of age but not at 12 - 15 or 18 months of age due to a decrease in wild-type circadian activity

abnormal sleep pattern ( J:150414 )

• shorter latency to behavioral signs of sleep, most prevalent at 4 -6 months of age

• difference in latency decreases with age due to a decrease in latency in wild-type mice with no difference detected at 24 months of age

nervous system

decreased dopaminergic neuron number ( J:123245 )

• reductions in striatal tyrosine hydroxylase-positive fiber density are seen at 18 and 22 months of age

• 12% and 26% cell loss is exhibited at 18 months and 24 months respectively in substantia nigra pars compacta

neuron degeneration ( J:123245 )

• increase in degenerating dopaminergic neurons are seem in substantia nigra pars compacta at 22 months compared to wild-type

alpha-synuclein inclusion body ( J:123245 )

• neurons in substantia nigra pars compacta show accumulation of alpha-synuclein at 18 and 22 months of age

abnormal nervous system physiology ( J:150414 )

• all major monoamines (dopamine, norepinephrine and serotonin) are reduced in all brain regions tested (striatum, cortex, and hippocampus)

• in general depletion of dopamine and norepinephrine are more severe than depletion of serotonin

• significant increase in the turnover of dopamine and serotonin

increased susceptibility to dopaminergic neuron neurotoxicity ( J:70606 )

• mice show enhanced sensitivity to MPTP relative to wild-type, displaying more dopamine cell loss in substantia nigra and ventral tegmental area

homeostasis/metabolism

increased susceptibility to dopaminergic neuron neurotoxicity ( J:70606 )

• mice show enhanced sensitivity to MPTP relative to wild-type, displaying more dopamine cell loss in substantia nigra and ventral tegmental area

decreased dopamine level ( J:70606 , J:123245 , J:150414 )

• at 3 to 6 months, dopamine levels are reduced in terminal and cell body regions, but without significant loss of dopamine cell bodies in substantia nigra or ventral tegmental area (J:70606)

• significantly reduced striatal dopamine levels, with increase in ratios of dopamine metabolites to dopamine in aged mice (J:123245)

• in all brain regions tested (striatum, cortex, and hippocampus) (J:150414)

abnormal noradrenaline level ( J:70606 , J:150414 )

• tissue levels are reduced (J:70606)

• reduced in all brain regions tested (striatum, cortex, and hippocampus) (J:150414)

decreased serotonin level ( J:70606 , J:150414 )

• tissue levels are reduced (J:70606)

• in all brain regions tested (striatum, cortex, and hippocampus) (J:150414)

taste/olfaction

impaired olfaction ( J:150414 )

• unable to discriminate between wooden block scented with either home cage bedding or bedding from the cage of a foreign mouse of the same sex at 5, 6, and 12 months of age

• treatment with L_DOPA does not improve olfaction

• deficits in nonsocial olfactory acuity (tested with lemon, vanilla, and peppermint) beginning at 3 months of age

digestive/alimentary system

increased defecation amount ( J:150414 )

• increase in stool frequency at 2 and 6 months of age

impaired gastric peristalsis ( J:150414 )

muscle

muscle phenotype ( J:150414 )

N • normal muscle strength

vision/eye

vision/eye phenotype ( J:150414 )

N • normal vision

cellular

increased susceptibility to dopaminergic neuron neurotoxicity ( J:70606 )

• mice show enhanced sensitivity to MPTP relative to wild-type, displaying more dopamine cell loss in substantia nigra and ventral tegmental area