Phenotypes associated with this allele

• Allele Symbol: Adra2c^tm1Gsb
• Allele Name: targeted mutation 1, Gregory S Barsh
• Allele ID: MGI:1857119
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adra2c^tm1Gsb/Adra2c^tm1Gsb	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J	MGI:3039694
hm2	Adra2c^tm1Gsb/Adra2c^tm1Gsb	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5508328
cx3	Adra2a^tm1Bkk/Adra2a^tm1Bkk Adra2b^tm1Gsb/Adra2b^tm1Gsb Adra2c^tm1Gsb/Adra2c^tm1Gsb	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J	MGI:3039647
cx4	Adra2a^tm1Bkk/Adra2a^tm1Bkk Adra2c^tm1Gsb/Adra2c^tm1Gsb	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J	MGI:3039688

Genotype
MGI:3039694

hm1

• Allelic Composition: Adra2c^tm1Gsb/Adra2c^tm1Gsb
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J

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

behavior/neurological

behavior/neurological phenotype ( J:38466 , J:46923 , J:49002 , J:89316 )

N • in response to dexmedetomidine, homozygous mutant mice displayed no major differences in spontaneous locomotor activity or its diurnal rhythm relative to wild-type (J:38466)

N • homozygous mutant mice displayed decreased attack latency in the isolation-induced aggression paradigm; however, there was no significant difference in the overall number of attacks, and preisolation aggressive behavior was normal (J:46923)

N • homozygous mutant mice showed no significant differences from wild-type mice in head twitches in response to dexmedetomidine (J:49002)

N • in response to dexmedetomidine, homozygous mutant mice showed normal dose-dependent reductions in locomotor activity (J:89316)

N • also, dexmedetomidine induced normal dose-dependent antinociception in homozygous mutant mice in the hot-water tail immersion test (J:89316)

abnormal spatial working memory ( J:53676 , J:89323 )

• homozygous mutant mice displayed attenuated performance in the T-maze delayed alternation task: in this paradigm, mutants showed normal dose-dependent reductions in non-perseverative errors and increased performance in response to dexmedetomidine (J:53676)

• homozygous mutant mice made more working memory errors after the change of the baited arm in radial arm maze; however, mutant and wild-type mice performed equally well after training (J:89323)

• dexmedetomidine attenuated the increase in spatial working memory errors after the change of the baited arm (J:89323)

• homozygous mutant and wild-type mice performed equally well in T-maze, and dexmedetomidine had no effect on this simple response learning (J:89323)

increased coping response ( J:59712 )

• homozygous mutant mice displayed decreased immobility in a modified version of Porsolt's forced swimming test, indicating attenuated behavioral despair

• also, homozygous mutants showed attenuated elevation of plasma corticosterone after different stressors

increased startle reflex ( J:46923 )

• homozygous mutant mice displayed enhanced startle responses, and diminished prepulse inhibition (PPI) of the startle reflex

cardiovascular system

cardiovascular system phenotype ( J:34819 )

N • compared with wild-type, adult homozygous mutant mice displayed no significant differences in the magnitude of the hypertensive, hypotensive, or bradycardic responses to dexmedetomidine, a highly selective alpha2-adrenergic receptor agonist

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:38466 , J:89316 )

N • contrary to original findings, homozygous null mice were reported to show a significant attenuation of the hypothermic response induced by dexmedetomidine (J:38466)

N • in response to dexmedetomidine, homozygous mutant mice showed normal dose-dependent reductions in body temperature (J:89316)

nervous system

nervous system phenotype ( J:38466 , J:49002 , J:58591 )

N • in response to dexmedetomidine, homozygous mutant mice displayed normal dose-dependent reductions in brain monoamine turnover, with the exception of some minor but consistent changes, including slightly reduced levels of metabolites of dopamine (homovanillic acid), norepinephrine (3-methoxy-4-hydroxyphenylglycol), and serotonin (5-hydroxyindoleacetic acid) (J:38466)

N • relative to wild-type mice, homozygous mutant mice displayed increased locomotor activity in response to amphetamine; this effect was more prominent in amphetamine-treated male mutants than in female mutants (J:49002)

N • notably, dexmedetomidine failed to attenuate symptoms of the 5-hydroxytryptophan-induced serotonin syndrome in homozygous mutant mice (J:49002)

N • in homozygous mutant mice, the maximal inhibitory effect of brimonidine on norepinephrine release was normal, relative to wild-type mice (J:58591)

Genotype
MGI:5508328

hm2

• Allelic Composition: Adra2c^tm1Gsb/Adra2c^tm1Gsb
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

nervous system phenotype ( J:197965 )

N • mice exhibit normal epinephrine-induced reduction in burst frequency of induced epileptiform activity

Genotype
MGI:3039647

cx3

• Allelic Composition: Adra2a^tm1Bkk/Adra2a^tm1Bkk; Adra2b^tm1Gsb/Adra2b^tm1Gsb; Adra2c^tm1Gsb/Adra2c^tm1Gsb
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:77486 )

• triple homozygous mutant embryos died between E9.5-E11.5

cardiovascular system

cardiovascular system phenotype ( J:77486 )

N • at E9.5, triple mutant embryos had a normal heart rate and a normal cardiac structure

decreased heart rate ( J:77486 )

• at E10.5, only moribund triple mutant embryos displayed bradycardia

• also, triple mutant embryos had normal concentrations of L-dopa and noradrenaline but exhibited a reduction in basal phosphorylation of mitogen activated protein kinase-1 and -3

embryo

abnormal visceral yolk sac morphology ( J:77486 )

• the yolk sac of triple homozygous mutant embryos was less vascularized and appeared more translucent relative to wild-type

• the endothelial cells in the yolk sac were often detached from the visceral endoderm cell layer

abnormal placenta development ( J:77486 )

• triple mutant mice displayed a significantly reduced density of fetal blood vessels in the placental vascular labyrinth, which leads to embryonic lethality as a result of limited oxygen and nutrient supply

Genotype
MGI:3039688

cx4

• Allelic Composition: Adra2a^tm1Bkk/Adra2a^tm1Bkk; Adra2c^tm1Gsb/Adra2c^tm1Gsb
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J

cardiovascular system

cardiac hypertrophy ( J:58591 )

• double homozygous mutant mice displayed increased plasma noradrenaline concentrations and developed cardiac hypertrophy with reduced left ventricular contractility by 4 months of age

nervous system

abnormal synaptic norepinephrine release ( J:58591 )

• the inhibitory effect of brimonidine on norepinephrine release was completely abolished in double homozygous mutant mice

• additional experiments in double homozygous mutant mice demonstrated that ADRA2A inhibits transmitter release at high stimulation frequencies, whereas ADRA2C regulates release at lower levels; both subtypes are, however, required for normal presynaptic control of neurotransmitter release from sympathetic nerves in the heart and from central noradrenergic neurons

growth/size/body

cardiac hypertrophy ( J:58591 )

• double homozygous mutant mice displayed increased plasma noradrenaline concentrations and developed cardiac hypertrophy with reduced left ventricular contractility by 4 months of age