Phenotypes Associated with This Genotype

Genotype
MGI:3629947

• Allelic Composition: Grm2^tm1Nak/Grm2^tm1Nak
• Genetic Background: B6.129S-Grm2^tm1Nak

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

nervous system

nervous system phenotype ( J:202321 )

N • astrocytes exhibit normal neuroprotection of LY379268 or MPEP treatment in culture experiments

decreased susceptibility to neuronal excitotoxicity ( J:202321 )

• NMDA neurotoxicity is reduced when neurons are cocultured with wild-type astrocytes compared with when wild-type astrocytes are cocultured with wild-type neurons

• systemic injection of LY379268 reduces nigrostriatal degeneration in MPTP-treated mice unlike in wild-type mice

• however, mice exhibit normal NMDA-induced toxicity and LY379268 protection to NMDA-induced neurotoxicity

abnormal GABAergic neuron physiology ( J:202321 )

• neurons treated with LY379268 fail to exhibit an inhibition of GABA release unlike wild-type cells

• LY379268-treatment reduced GABA release unlike in wild-type neurons

• however, glutamate release is normally affected by LY379268-treatment

behavior/neurological

cocaine preference ( J:97172 )

• increased addictive behaviors in response to cocaine

abnormal motor capabilities/coordination/movement ( J:97172 )

impaired coordination ( J:97172 )

• impaired ability to maintain balance on an accelerating rotarod

increased locomotor activity ( J:97172 )

• distance traveled is significantly greater than controls when first exposed to open field test but not after 3 day habituation to environment

• similar results in light/dark transition tests, elevated maze, and social interaction tests but to a lesser degree

• higher mobility on second and subsequent days of testing in a forced swim test

homeostasis/metabolism

decreased susceptibility to neuronal excitotoxicity ( J:202321 )

• NMDA neurotoxicity is reduced when neurons are cocultured with wild-type astrocytes compared with when wild-type astrocytes are cocultured with wild-type neurons

• systemic injection of LY379268 reduces nigrostriatal degeneration in MPTP-treated mice unlike in wild-type mice

• however, mice exhibit normal NMDA-induced toxicity and LY379268 protection to NMDA-induced neurotoxicity

increased dopamine level ( J:97172 )

• significantly greater increase in extracellular dopamine and glutamate after cocaine administration

cellular

decreased susceptibility to neuronal excitotoxicity ( J:202321 )

• NMDA neurotoxicity is reduced when neurons are cocultured with wild-type astrocytes compared with when wild-type astrocytes are cocultured with wild-type neurons

• systemic injection of LY379268 reduces nigrostriatal degeneration in MPTP-treated mice unlike in wild-type mice

• however, mice exhibit normal NMDA-induced toxicity and LY379268 protection to NMDA-induced neurotoxicity