Phenotypes associated with this allele

• Allele Symbol: Slc6a2^tm1Mca
• Allele Name: targeted mutation 1, Marc G Caron
• Allele ID: MGI:2386278
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc6a2^tm1Mca/Slc6a2^tm1Mca	B6.129S4-Slc6a2^tm1Mca	MGI:3852392
hm2	Slc6a2^tm1Mca/Slc6a2^tm1Mca	involves: 129S4/SvJaeSor	MGI:3029342
hm3	Slc6a2^tm1Mca/Slc6a2^tm1Mca	involves: 129S4/SvJaeSor * C57BL/6J	MGI:3029328

Genotype
MGI:3852392

hm1

• Allelic Composition: Slc6a2^tm1Mca/Slc6a2^tm1Mca
• Genetic Background: B6.129S4-Slc6a2^tm1Mca

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

nervous system

enhanced long-term potentiation ( J:89778 )

• significant enhancement of long term potentiation in a minimal tetanus assay

Genotype
MGI:3029342

hm2

• Allelic Composition: Slc6a2^tm1Mca/Slc6a2^tm1Mca
• Genetic Background: involves: 129S4/SvJaeSor

behavior/neurological

decreased vertical activity ( J:66729 )

• significant reduction in basal levels of vertical activity when exposed to a new environment

decreased locomotor activity ( J:66729 )

• significant reduction in basal levels of horizontal activity when exposed to a new environment

increased chemically-elicited antinociception ( J:66729 )

• significantly greater morphine-induced spinal analgesia than wild-type controls in the tail-flick assay at 10 and 20 mg/kg morphine (s.c.), as determined by tail-flick (54 degrees C) response latencies

• dramatically greater endogenous opioid-mediated analgesia than wild-type controls in the tail-flick assay after a warm (30-33 degrees C) water swim

increased thermal nociceptive threshold ( J:66729 )

• modest but significant increase in tail withdrawal latency in warm water (54C) tail-flick assay, indicating an increased basal spinal nociceptive threshold relative to wild-type controls

• in contrast, hot plate (56 degrees C) paw withdrawal latency is similar to that in wild-type controls

homeostasis/metabolism

abnormal noradrenaline level ( J:66729 )

• 50% decrease of norepinephrine (NE) content in spinal cord tissue, suggesting increased extracellular NE levels relative to wild-type controls

• >50% decrease in alpha1-AR number in spinal cord membrane preparations, consistent with increased NE levels in spinal cord

abnormal physiological response to xenobiotic ( J:66729 )

• yohimbine, an alpha2-adrenergic receptor (AR) antagonist, reverses the enhanced morphine analgesia to the same extent seen in wild-type mice after morphine treatment alone, but has no effect on analgesia in morphine-treated wild-type mice

• desipramine (DMI), a tricyclic antidepressants, enhances morphine analgesia in wild-type mice but has no apparent effect on morphine analgesia in mutant mice, as measured by tail-flick latencies; however, DMI is still able to significantly depresses both horizontal and vertical activities in mutant mice

Genotype
MGI:3029328

hm3

• Allelic Composition: Slc6a2^tm1Mca/Slc6a2^tm1Mca
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6J

behavior/neurological

enhanced behavioral response to addictive substance ( J:61825 )

• mice were hyper-responsive to locomotor stimulation by cocaine and amphetamine

enhanced behavioral response to cocaine ( J:61825 )

• mice were hyper-responsive to locomotor stimulation by cocaine

abnormal emotion/affect behavior ( J:61825 )

• the behavior of untreated mice was similar to that of wild-type mice treated with antidepressants

growth/size/body

decreased body weight ( J:61825 )

• 20% reduction relative to wild-type

homeostasis/metabolism

decreased body temperature ( J:61825 )

• body temperature reduced by approximately 1 degree celsius relative to wild-type

increased physiological sensitivity to xenobiotic ( J:61825 )

• behavioral hypersensitivity was accompanied by dopamine D₂/D₃ receptor supersensitivity

nervous system

abnormal nervous system physiology ( J:61825 )

• increased extracellular levels of norepinephrine due to prolonged clearance by presynaptic noradrenergic neurons