Phenotypes Associated with This Genotype

Genotype
MGI:6270171

• Allelic Composition: Tg(Camk2a-Polg*D181A)BTkato/0
• Genetic Background: C57BL/6J-Tg(Camk2a-Polg*D181A)BTkato

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

growth/size/body

decreased body weight ( J:127895 )

• mice weigh about 10% less than controls, however there is no difference in food intake per body weight suggesting that lower weight is due to reduced food intake

behavior/neurological

behavior/neurological phenotype ( J:127895 )

♂N • 22-29 week old males exhibit normal motor coordination and normal fatigue resistance in the rotarod and treadmill tests

♂N • 18-27 week old males show normal ambulatory activity in the open field test, normal grooming, rearing, jumping, defecation and urination, and normal behavior in the elevated plus-maze test, no differences in the immobility time in the forced swimming test, in the novel-object recognition test, and in conditioned fear learning test

decreased food intake ( J:127895 )

♂ • 21-28 week old males eat less than wild-type mice

increased fear-related response ( J:127895 )

♂ • mice exhibit increased freezing in the conditioning phase of the fear-learning test but no other differences in this test

increased startle reflex ( J:127895 )

♂ • the amplitude of the acoustic startle response is increased in 18-27 week old males

abnormal voluntary movement ( J:127895 )

• total wheel running activity is decreased

abnormal ultradian rhythm behavior ( J:127895 )

• mice exhibit altered intra-day activity rhythm, characterized by prolonged activity duration such as delayed and anticipatory activity; longer duration of activity is accompanied by lower intensity of activity

• however, mice do not show impairment in the circadian clock machinery

• chronic treatment with a tricyclic antidepressant, amitriptyline, induces manic switch-like behavior in some mice and worsens the distorted day-night rhythm; mice continue to show increased activity after termination of treatment indicating long-lasting influence of the drug

• females exhibit estrous cycle-associated fluctuation in wheel-running activity that is most prominent around 30-40 weeks after birth and disappears over 60 weeks of age

• lithium treatment improves the periodic activity change associated with the estrous cycle in females and the distorted day-night rhythm, but has no effect on the level of wheel-running activity

homeostasis/metabolism

abnormal dopamine level ( J:127895 )

♂ • 22-32 week old males exhibit increased dopamine (DA) levels in the hippocampus and decreased DA levels in the amygdala

♂ • dopamine levels, assessed by 3,4-dihydroxyphenylacetic acid (DOPAC)/DA or homovanillic acid (HVA/DA) ratios, are increased in the amygdala and decreased in the hippocampus of 22-32 week old males

decreased noradrenaline level ( J:127895 )

♂ • 22-32 week old males exhibit decreased noradrenaline levels

decreased serotonin level ( J:127895 )

♂ • 22-32 week old males exhibit a 67% and 86% decrease in serotonin (5-HT) levels in the amygdala and hippocampus, respectively

♂ • serotonin turnover is increased in the amygdala and hippocampus of 22-32 week old males

cellular

abnormal mitochondrial chromosome morphology ( J:127895 )

• mice exhibit mtDNA defects in the brain, with 68 week old mice showing deleted mtDNAs of about 2 kb

• small mtDNAs accumulate first in the hippocampus and cortex at 17 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
bipolar disorder		DOID:3312		J:127895
mood disorder		DOID:3324		J:127895