Phenotypes associated with this allele

• Allele Symbol: Slc6a3^tm1Mca
• Allele Name: targeted mutation 1, Marc G Caron
• Allele ID: MGI:2386303
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc6a3^tm1Mca/Slc6a3^tm1Mca	B6.129P2-Slc6a3^tm1Mca	MGI:3852393
hm2	Slc6a3^tm1Mca/Slc6a3^tm1Mca	involves: 129P2/OlaHsd	MGI:2654500
hm3	Slc6a3^tm1Mca/Slc6a3^tm1Mca	involves: 129P2/OlaHsd * C57BL/6	MGI:4429895
hm4	Slc6a3^tm1Mca/Slc6a3^tm1Mca	involves: 129P2/OlaHsd * C57BL/6J	MGI:3056098
cx5	Slc6a3^tm1Mca/Slc6a3^tm1Mca Slc6a4^tm1Kpl/Slc6a4^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:3056097
cx6	Slc6a3^tm1Mca/Slc6a3^tm1Mca Slc6a4^tm1Kpl/Slc6a4^tm1Kpl	involves: 129P2/OlaHsd * C57BL/6J	MGI:3056096
cx7	Mlca4^C57BL/6J/? Slc6a3^tm1Mca/Slc6a3^+	involves: C57BL/6J * DBA/2J	MGI:3702110
cx8	Mlca5^DBA/2J/? Slc6a3^tm1Mca/Slc6a3^+	involves: C57BL/6J * DBA/2J	MGI:3702111

Genotype
MGI:3852393

hm1

• Allelic Composition: Slc6a3^tm1Mca/Slc6a3^tm1Mca
• Genetic Background: B6.129P2-Slc6a3^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:2654500

hm2

• Allelic Composition: Slc6a3^tm1Mca/Slc6a3^tm1Mca
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:31328 )

• 68% survival after 10 wks

growth/size/body

decreased body size ( J:109373 )

• mutants are smaller than wild-type; femur length is 1.46 cm in adult mutants and 1.55 cm in wild-type adult animals, whereas length is 1.46 cm in 6-week old wild-type

decreased body weight ( J:41856 )

• reduced weight apparent by 1 week of age with a 44% reduction in body weight relative to wild-type by 8 weeks

disproportionate dwarf ( J:41856 )

postnatal growth retardation ( J:31328 , J:41856 )

• homozygotes exhibit slower rate of weight gain than wild-type mice, and remain lighter than wild-type through 10 weeks of age (J:31328)

• mutant mice raised by foster mothers exhibited slower rates of growth than wild-type mice (J:41856)

behavior/neurological

abnormal spatial learning ( J:79011 )

• mutants show impaired learning in radial arm maze tests

increased thigmotaxis ( J:109373 )

• time spent in central compartment is decreased by 87.5% and time per visit is decreased by 86.1% relative to wild-type

impaired coordination ( J:109373 )

• 5adult (18-24 weeks of age) mice tend to spend slightly less time on the rotating rod than wild-type, and acquisition of maximal performance appears to be slower in mutant animals

• in a pole test, mutants display dramatically impaired performance on the T-turn (time increased 692%) and the T-total (time increased 552%) compared to wild-type

short stride length ( J:109373 )

• decrease in both fore- and hind-limb stride lengths (decrease of 18.1% and 15.4% respectively) is observed relative to adult mice; stride lengths are significantly different from 6-week old wild-type mice, showing that femur length is not cause for difference.

decreased vertical activity ( J:109373 )

• 29.2% fewer rearing movements relative to wild-type

increased locomotor activity ( J:31328 , J:79011 , J:109373 )

• naive homozygous mice exhibit highly elevated spontaneous locomotor activity, with a 2-fold increased half-time of habituation, and are 5-6-fold more active during both phases of the light-dark cycle compared to wild-type (J:31328)

• mice exhibit spontaneous hyperlocomotor activity similar to that displayed by wild-type mice administered maximal doses of cocaine or amphetamine (J:31328)

• in novel environment, animals exhibit much higher activity levels than wild-type, and show little habituation after 4 hours whereas wild-type habituate in 20-40 minutes (J:79011)

• hyperactivity was suppressed by the administration of psychostimulants (J:79011)

• mice show hyperactivity with increased velocity and distance traveled compared to wild-type (J:109373)

abnormal maternal nurturing ( J:31328 )

♀ • females show impaired maternal behavior such that offspring survival partially dependent on transfer to foster mother

nervous system

abnormal adenohypophysis morphology ( J:41856 )

• reduced density and distribution of lactotrophs and somatotrophs

• unaffected density and distribution of thyrotrophs and gonadotrophs

decreased lactotroph cell number ( J:41856 )

• selective decrease in pituitary

decreased somatotroph cell number ( J:41856 )

• selective decrease in pituitary

adenohypophysis hypoplasia ( J:41856 )

• at 4 and 8 weeks of age, anterior lobe is ~50% of normal weight

pituitary intermediate lobe hypoplasia ( J:41856 )

• at 4 and 8 weeks of age, intermediate lobe is ~50% of normal weight

abnormal pituitary gland physiology ( J:41856 )

• growth hormone-releasing hormone, GHRH content in pituitary is decreased by 43% relative to wild-type mice

abnormal pituitary secretion ( J:41856 )

• 85% reduction in level of prolactin in pituitary gland, though plasma prolactin levels were normal

• 70% reduction in level of growth hormone in pituitary gland, though plasma growth hormone levels were normal

hypopituitarism ( J:41856 )

decreased dopaminergic neuron number ( J:59670 , J:109373 )

• decreased number of dopa decarboxylase- and tyrosine hydroxylase-labeled neurons in the substantia nigra pars compacta and ventral tegmental area is detected (J:59670)

• small, significant decrease in neuronal density in anterior striatum is seen compared to wild-type (J:109373)

endocrine/exocrine glands

abnormal adenohypophysis morphology ( J:41856 )

• reduced density and distribution of lactotrophs and somatotrophs

• unaffected density and distribution of thyrotrophs and gonadotrophs

decreased lactotroph cell number ( J:41856 )

• selective decrease in pituitary

decreased somatotroph cell number ( J:41856 )

• selective decrease in pituitary

adenohypophysis hypoplasia ( J:41856 )

• at 4 and 8 weeks of age, anterior lobe is ~50% of normal weight

pituitary intermediate lobe hypoplasia ( J:41856 )

• at 4 and 8 weeks of age, intermediate lobe is ~50% of normal weight

abnormal pituitary gland physiology ( J:41856 )

• growth hormone-releasing hormone, GHRH content in pituitary is decreased by 43% relative to wild-type mice

abnormal pituitary secretion ( J:41856 )

• 85% reduction in level of prolactin in pituitary gland, though plasma prolactin levels were normal

• 70% reduction in level of growth hormone in pituitary gland, though plasma growth hormone levels were normal

hypopituitarism ( J:41856 )

lactation failure ( J:41856 )

♀ • females cannot lactate postpartum

skeleton

decreased length of long bones ( J:41856 )

• reduction in the length of long bones

integument

lactation failure ( J:41856 )

♀ • females cannot lactate postpartum

homeostasis/metabolism

decreased dopamine level ( J:31328 , J:41856 , J:59670 , J:79010 )

• evoked release of dopamine from caudate brain slices produces an extracellular concentration of 1.1 um compared to 4.1 um in wild-type slices (J:31328)

• pituitary dopamine content is decreased by ~35% and hypothalamic tissue dopamine content is reduced by 30% relative to wild-type (J:41856)

• level of dopamine in ventral midbrain and striatum is extensively decreased (J:59670)

• dopamine persists in the extracellular space 300 times longer than in wild-type mice, but extracellular levels are only 5-fold greater than in wild-type (J:79010)

• 95% reduction of intracellular dopamine and 75% reduction in release, but rate of synthesis is doubled (J:79010)

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:79011
schizophrenia		DOID:5419	OMIM:181500	J:31328

Genotype
MGI:4429895

hm3

• Allelic Composition: Slc6a3^tm1Mca/Slc6a3^tm1Mca
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:110704 )

N • mice exhibit normal novel odor habituation, odor sensitivity, long-term habituation, and memory for a single odor

N • mice exhibit normal tactile responsivity, trigeminal nerve response, or aversive taste reactivity

abnormal response to novel odor ( J:110704 )

• mice fail to exhibit an increase in investigation of a novel odor unlike wild-type mice

• mice exhibit an impairment in olfactory discrimination compared with wild-type mice

• mice fail to exhibit increased investigation of an object with a novel scent versus one with s familiar scent unlike wild-type mice

• however, mice exhibit normal exploration behavior

nervous system

nervous system phenotype ( J:110704 )

N • mice exhibit normal olfactory bulb neurogenesis

taste/olfaction

taste/olfaction phenotype ( J:110704 )

N • mice exhibit normal novel odor habituation, odor sensitivity, long-term habituation, and memory for a single odor

Genotype
MGI:3056098

hm4

• Allelic Composition: Slc6a3^tm1Mca/Slc6a3^tm1Mca
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

behavior/neurological

increased exploration in new environment ( J:93114 )

• movement in a novel environment is increased compared to wild-type

endocrine/exocrine glands

abnormal adenohypophysis morphology ( J:93114 )

• abnormal central anterior pituitaries with fewer acidophilic cells are seen

small pituitary gland ( J:93114 )

• small pituitary glands

growth/size/body

postnatal growth retardation ( J:93114 )

• homozygotes grow slowly compared to wild-type

nervous system

abnormal adenohypophysis morphology ( J:93114 )

• abnormal central anterior pituitaries with fewer acidophilic cells are seen

small pituitary gland ( J:93114 )

• small pituitary glands

Genotype
MGI:3056097

cx5

• Allelic Composition: Slc6a3^tm1Mca/Slc6a3^tm1Mca; Slc6a4^tm1Kpl/Slc6a4⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

behavior/neurological

impaired conditioned place preference behavior ( J:93114 )

• mutants do not display any cocaine place preference

Genotype
MGI:3056096

cx6

• Allelic Composition: Slc6a3^tm1Mca/Slc6a3^tm1Mca; Slc6a4^tm1Kpl/Slc6a4^tm1Kpl
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

behavior/neurological

impaired conditioned place preference behavior ( J:93114 )

• double homozygotes do not display any cocaine place preference

increased exploration in new environment ( J:93114 )

• movement in a novel environment is increased compared to wild-type and Slc6a3^tm1Mca homozygotes

endocrine/exocrine glands

abnormal adenohypophysis morphology ( J:93114 )

• abnormal central anterior pituitaries with fewer acidophilic cells are seen similar to Slc6a3^tm1Mca homozygotes

small pituitary gland ( J:93114 )

• small pituitary glands are seen similar to Slc6a3^tm1Mca homozygotes

growth/size/body

postnatal growth retardation ( J:93114 )

• double homozygotes grow slower than wild-type but not as slowly as Slc6a3^tm1Mca homozygotes

nervous system

abnormal adenohypophysis morphology ( J:93114 )

• abnormal central anterior pituitaries with fewer acidophilic cells are seen similar to Slc6a3^tm1Mca homozygotes

small pituitary gland ( J:93114 )

• small pituitary glands are seen similar to Slc6a3^tm1Mca homozygotes

Genotype
MGI:3702110

cx7

• Allelic Composition: Mlca4^C57BL/6J/?; Slc6a3^tm1Mca/Slc6a3⁺
• Genetic Background: involves: C57BL/6J * DBA/2J

behavior/neurological

increased locomotor activity ( J:118059 )

• increased spontaneous locomotor activity

Genotype
MGI:3702111

cx8

• Allelic Composition: Mlca5^DBA/2J/?; Slc6a3^tm1Mca/Slc6a3⁺
• Genetic Background: involves: C57BL/6J * DBA/2J

behavior/neurological

increased locomotor activity ( J:118059 )

• increased spontaneous locomotor activity