Phenotypes Associated with This Genotype

Genotype
MGI:6314222

• Allelic Composition: Atp1a2^tm1.1Tmklh/Atp1a2⁺
• Genetic Background: B6.129S1(Cg)-Atp1a2^tm1.1Tmklh

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

behavior/neurological

abnormal emotion/affect behavior ( J:259556 )

♀ • females exhibit more distressed behaviors in the open field such as increased dropping and urination compared to wild-type mice

anhedonia ( J:259556 )

• mice show anhedonia in the sucrose-preference test when short- or long-lasting stress protocols are applied prior to the test

• however, unstressed mice exhibit normal sucrose-preference

behavioral despair ( J:259556 )

• in the tail suspension test, mice exhibit a stress-induced depression-like phenotype, displaying increased immobility, reduced mobility, reduced movement, and fewer rotations than wild-type mice

increased grooming behavior ( J:259556 )

♀ • females display increased grooming compared to wild-type mice

♀ • treatment of females with Depoprovera reduces the excessive grooming behavior

abnormal impulsive behavior control ( J:259556 )

♀ • females exhibit increased marble-burying behavior

♀ • treatment of females with amantadine or memantine or Depoprovera rescues the increased marble-burying behavior

♀ • however, mice exhibit normal behavior in the elevated plus maze indicting no anxiety

increased startle reflex ( J:259556 )

• both males and females show increased responsivity to aversive acoustic stimuli

• mice administered the weak NMDA type glutamate receptor antagonist amantadine show rescue of the increased acoustic startle reflex

impaired coordination ( J:259556 )

♀ • females spend less time on the accelerated rotarod indicating decreased endurance, learning and coordination

♀ • however, grip strength is normal

♀ • treatment of female mice with Depoprovera, a progestin-only contraceptive, rescues rotarod behaviors seen in females

decreased locomotor activity ( J:259556 )

♀ • females exhibit hypolocomotion as they travel a shorter distance and move more slowly than wild-type females

♀ • treatment of female mice with Depoprovera, a progestin-only contraceptive, rescues the open field behaviors seen in females

abnormal social investigation ( J:259556 )

• in the three-chamber sociability test, mice show reduced sociability and spend comparable amounts of time in both chambers and comparable sniffing times to the stranger mouse and the empty cage and have the same number of entries into both chambers

excessive vocalization ( J:259556 )

• in the tail suspension test, about 50% of mice emit audible squeaks compared to about 14% of wild-type mice

growth/size/body

increased body weight ( J:259556 )

♂ • males gain more weight over a period of 4 months than wild-type males

♂ • however, females show normal body weight progression

homeostasis/metabolism

increased glutamic acid level ( J:259556 )

♀ • females exhibit elevated glutamate levels in the cortex, hippocampus, and cerebellum

♀ • treatment of females with Depoprovera reduces glutamate levels to wild-type levels

♀ • mice show normal levels of dopamine, noradrenaline, serotonin and GABA in frontal and occipital cortex, striatum, hippocampus, brain stem, and cerebellum

nervous system

abnormal nervous system electrophysiology ( J:259556 )

♂ • recovery phase after cortical spreading depression is prolonged in males

♂ • however, cerebral blood flow is similar to wild-type after cortical spreading depression induction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hemiplegic migraine 2		DOID:0111182	OMIM:602481	J:259556