Phenotypes Associated with This Genotype

Genotype
MGI:2654522

• Allelic Composition: Slc6a3^tm2Mca/Slc6a3^tm2Mca
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

behavior/neurological

increased exploration in new environment ( J:67549 )

• homozygotes display overall hyperactivity in both path length and rearing activity measures and decreased response habituation in novel environments relative to wild-type controls

abnormal response to novel object ( J:67549 )

• in the novel object exploration test, homozygotes show increased exploratory activity toward a novel object placed in the center of an open field relative to wild-type controls

• in the Y-maze test, homozygotes exhibit impaired exploratory preference for the novel arm after a short habituation in other arms: when first allowed to explore two arms for 10 min, homozygotes fail to spend most of the 5-min test period exploring a newly introduced arm; however, both genotypes spend most of their time in the new arm when habituation time in the first two arms was increased to 60 min

abnormal grooming behavior ( J:176799 )

• mutants exhibit a pattern of more stereotyped and syntactic grooming sequences

• mutants spend 10-50% more time than wild-type mice in grooming behavior

• the increased time spent grooming is due to longer grooming bouts and not due to a greater number of bouts when in the home cage

• the increased time spent grooming is due to a greater number of grooming bouts but not longer bouts when in the laboratory environment

• mutants in home cages have longer cumulative durations of body licking compared to controls

increased vertical activity ( J:67549 )

• homozygotes show an overall higher rearing activity after habituation to a novel environment (open field) relative to wild-type controls

• however, homozygotes show normal rearing activity during the initial open-field exposure relative to controls

increased locomotor activity ( J:67549 )

• homozygotes show an overall higher locomotor activity after habituation to a novel environment (open field) relative to wild-type controls

• however, homozygotes show normal home cage behavior as well as normal locomotor activity during the initial open-field exposure relative to controls

increased stereotypic behavior ( J:176799 )

• mutants exhibit a pattern of more stereotyped and syntactic grooming sequences (sequential super-stereotypy) that resist disruption compared to wild-type mice

• mutants initiate about 5% and 25% more syntactic grooming chains in the home cage environment and laboratory environment, respectively, than wild-type mice, indicating that stress initiates mutants to begin stereotyped behavior

• mutants are more likely than wild-type mice to complete the syntactic chain patterns that they start

homeostasis/metabolism

increased dopamine level ( J:67549 )

• homozygotes exhibit a chronic hyperdopaminergic tone, with a 70% increase in extracellular striatal dopamine relative to wild-type controls

• homozygotes display higher 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid (HVA)/dopamine ratios than wild-type controls, indicating an increased dopamine turnover

abnormal physiological response to xenobiotic ( J:67549 )

• all administered doses of amphetamine (an indirect dopamine agonist), apomorhine (a mixed D1/D2 agonist), and quinpirole (a D2-selective agonist) are shown to inhibit locomotor activities in mutant mice, unlike in wild-type controls where amphetamine increases locomotor activities in a dose-dependent fashion while apomorphine and quinpirole have an inhibitory effect at low doses, but an excitatory effect at high doses

• in addition, the locomotor stimulatory effect of SKF-81297 (a D1-selective agonist) is reduced relative to that in wild-type controls

nervous system

nervous system phenotype ( J:67549 )

N • adult homozygotes do not display anterior pituitary hypoplasia or defects in pituitary gross anatomy

decreased neurotransmitter release ( J:67549 )

• homozygotes show a ~75% reduction in dopamine release, due to impaired dopamine recycling leading to a reduced pool of releasable dopamine

• electrically stimulated dopamine release is cleared at a much slower rate than in wild-type controls

• homozygotes display a ~55% decrease in total tissue dopamine content relative to wild-type controls, consistent with diminished dopamine release

growth/size/body

growth/size/body region phenotype ( J:67549 )

N • homozygotes are viable, fertile and do not display postnatal growth retardation relative to wild-type control littermates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
attention deficit hyperactivity disorder		DOID:1094	OMIM:143465 OMIM:608903 OMIM:608904 OMIM:608905 OMIM:608906 OMIM:612311 OMIM:612312	J:67549
Gilles de la Tourette syndrome		DOID:11119	OMIM:137580	J:176799