Phenotypes associated with this allele

• Allele Symbol: Slc6a1^tm1Mlit
• Allele Name: targeted mutation 1, Jian Fei
• Allele ID: MGI:3832387
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc6a1^tm1Mlit/Slc6a1^tm1Mlit	B6.129S1-Slc6a1^tm1Mlit	MGI:5559028
hm2	Slc6a1^tm1Mlit/Slc6a1^tm1Mlit	involves: 129S1/Sv * C57BL/6	MGI:3832407
ht3	Slc6a1^tm1Mlit/Slc6a1^+	involves: 129S1/Sv * C57BL/6	MGI:3832408

Genotype
MGI:5559028

hm1

• Allelic Composition: Slc6a1^tm1Mlit/Slc6a1^tm1Mlit
• Genetic Background: B6.129S1-Slc6a1^tm1Mlit

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

behavior/neurological

enhanced behavioral response to xenobiotic ( J:204368 )

• mice show increased sensitivity to psychotomimetic drugs, MK801 and PCP

• antipsychotic drugs, haloperidol, clozapine, and risperidone, reduce locomotor activity to a greater extent than in wild-type mice, indicating increased sensitivity to antipsychotic drugs

impaired cued conditioning behavior ( J:204368 )

• cued fear memory is impaired, with increased freezing compared to wild-type mice

• pre-exposure to cue without shock does not reduce the cued fear memory as in wild-type mice

abnormal latent inhibition of conditioning behavior ( J:204368 )

• latent inhibition is impaired

abnormal object recognition memory ( J:204368 )

• in an object recognition test, mice do not show a greater preference for the new object as seen in wild-type mice indicating impaired object recognition memory

impaired spatial working memory ( J:204368 )

• in the Morris water maze, mutants do not show a decline in the latency in finding the platform within the four trials as in wild-type mice, indicating impaired spatial working memory

• in the Y-maze, adult mice exhibit more total arm entries than wild-type mice, and less spontaneous alternation but more alternate arm returns, indicating impaired working memory

• young mice exhibit more total arm entries, less spontaneous alternation and more alternate arm returns in the Y-maze, indicating impaired working memory at an early age

• the GABAergic antagonist PTX improves working memory in mutants

abnormal response to novel object ( J:204368 )

• mice spend more time in the proximity of two new objects than wild-type mice, indicating exaggerated responses to novel objects

increased locomotor activity ( J:204368 )

• adult and young (4-5 weeks of age) mice show higher locomotor activity in the open field test than wild-type mice

• adult mice show locomotor hyperactivity in both short-term and long-term habituation tests

• antipsychotic drugs, haloperidol, clozapine, and risperidone, reduce locomotor activity to a greater extent than in wild-type mice, indicating increased sensitivity to antipsychotic drugs

• the GABAergic antagonist PTX reduces locomotor activity in mutants

abnormal social/conspecific interaction behavior ( J:204368 )

• young mice show abnormal social behaviors, showing a larger number of scattered cotton particles in the cages than wild-type mice

nervous system

nervous system phenotype ( J:204368 )

N • mice show normal striatal dopamine levels

reduced sensorimotor gating ( J:204368 )

• percent prepulse inhibition is lower than in wild-type mice, indicating impaired sensorimotor gating

abnormal GABA-mediated receptor currents ( J:204368 )

• the GABA antagonist PTX induces a tonic current in mutant prefrontal cortex unlike in wild-type mice in which PTX fails to induce any tonic current, and amplitudes of sIPSCs are smaller in mutants but the decay time is prolonged, indicating enhanced tonic GABA currents in prefrontal cortex

decreased prepulse inhibition ( J:204368 )

• percent prepulse inhibition is lower than in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
schizophrenia		DOID:5419	OMIM:181500	J:204368

Genotype
MGI:3832407

hm2

• Allelic Composition: Slc6a1^tm1Mlit/Slc6a1^tm1Mlit
• Genetic Background: involves: 129S1/Sv * C57BL/6

growth/size/body

decreased body weight ( J:144919 )

• mice have lower body weights but gradually normalize by 3-4 months of age

taste/olfaction

abnormal bitter taste sensitivity ( J:144919 )

• mice demonstrate an increased aversion than controls to water containing 0.03 mM or higher quinine

behavior/neurological

abnormal behavioral response to xenobiotic ( J:144919 )

• when a large dose (3.6 g/kg bodyweight) of ethanol is used as an anesthetic, mice exhibit significantly more tolerance to the sedative effects

• the time to regain righting reflex after ethanol administration is 51 minutes compared to 87 minutes for controls

abnormal conditioned taste aversion behavior ( J:144919 )

• mice have significantly reduced conditioned taste aversion for ethanol than do controls

increased startle reflex ( J:144919 )

• mice have a nervous-like behavior

tremors ( J:144919 )

• mice have strong body tremors when picked up or when encountering novel stimuli

ataxia ( J:144919 )

• is noted in these mice

hyperactivity ( J:144919 )

• mice have increased activity compared to controls

Genotype
MGI:3832408

ht3

• Allelic Composition: Slc6a1^tm1Mlit/Slc6a1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

taste/olfaction

abnormal bitter taste sensitivity ( J:144919 )

• mice demonstrate an increased aversion than controls to water containing 0.03 mM or higher quinine

behavior/neurological

alcohol preference ( J:144919 )

• mice have a higher preference ratio than controls for 9%, 12%, and 15% ethanol

increased alcohol consumption ( J:144919 )

• mice consume about a gram more (per kg bodyweight) of 9%, 12%, and 15% ethanol than controls

hyperactivity elicited by ethanol administration ( J:144919 )

• 2 g/kg bodyweight of ethanol induces a strong motor activation compared to a weak increase in wild-type controls

abnormal conditioned taste aversion behavior ( J:144919 )

• mice have significantly reduced conditioned taste aversion for ethanol than do controls

abnormal contextual conditioning behavior ( J:144919 )

• mice display significantly higher preference for ethanol-paired compartments than for saline paired compartments when first conditioned with saline or ethanol in either a striped- or grid- decorated compartment

saccharin preference ( J:144919 )

• mice have increased preference and consumption for water bottles containing saccharin

decreased locomotor activity ( J:144919 )

• mice have reduced activity compared to wild-type controls