Mouse Genome Informatics
hm1
    Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• unlike in wild-type mice, hyperglycemia cannot be induced by treatment with 3-iodothyronamine and/or 6-OH dopamine
• following treatment with 3-iodothyronamine


Mouse Genome Informatics
hm2
    Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• resting heart rate more than 180 beats/min greater than normal
• unlike wild-type controls, administration of the hypotensive agonist, dexmedetomidine, did not reduce blood pressure

nervous system
• increased release at high frequency electrical stimulation
• decreased release at low frequency electrical stimulation


Mouse Genome Informatics
hm3
    Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice treated with epinephrine fail to reduce burst frequency of induced epileptiform activity unlike in control mice

nervous system
• mice treated with epinephrine fail to reduce burst frequency of induced epileptiform activity unlike in control mice


Mouse Genome Informatics
cx4
    Adra2atm1Bkk/Adra2atm1Bkk
Adra2btm1Gsb/Adra2btm1Gsb
Adra2ctm1Gsb/Adra2ctm1Gsb

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• triple homozygous mutant embryos died between E9.5-E11.5

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

embryogenesis
• 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
• 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


Mouse Genome Informatics
cx5
    Adra2atm1Bkk/Adra2atm1Bkk
Adra2ctm1Gsb/Adra2ctm1Gsb

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 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
• 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