Phenotypes Associated with This Genotype

Genotype
MGI:6473973

• Allelic Composition: Gpr139^{tm1.1(KOMP)Vlcg}/Gpr139^{tm1.1(KOMP)Vlcg}
• Genetic Background: involves: C57BL/6NTac
• Cell Lines: 10338B-A5

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

nervous system

abnormal nervous system electrophysiology ( J:280704 )

• basal firing rates are selectively increased in locus coeruleus (LC) neurons but not in medial habenula (MHb) neurons

• firing of MHb neurons is significantly reduced by DAMGO (a synthetic enkephalin-mimetic peptide) at a low concentration (0.3 um), which has no significant effect in wild-type MHb neurons

• MHb neurons show a significantly greater net inhibition of neuronal firing by DAMGO both at a low (0.3 um) and high (1 uM) concentration

• following washout of DAMGO (1 uM), recovery kinetics of MHb neurons is significantly slower than that in wild-type MHb neurons, indicating greater susceptibility to opioid inhibition

• firing of LC neurons is significantly reduced by morphine at 0.1 um, which has no significant effect in wild-type LC neurons

behavior/neurological

behavior/neurological phenotype ( J:280704 )

N • at ~4 months of age, mice exhibit normal baseline learning, nociception, locomotor activity, habituation to an unfamiliar environment and motor coordination relative to wild-type controls

decreased behavioral withdrawal response ( J:280704 )

• mice exhibit significantly reduced withdrawal signs (diarrhea, jumps, dog shakes, paw tremor, back walking, tremor and ptosis) and weight loss due to naloxone-precipitated somatic withdrawal after chronic morphine exposure

enhanced conditioned place preference behavior ( J:280704 )

• in a conditioned place preference paradigm, mice exhibit augmented responses to the rewarding effects of morphine, in agreement with increased opioid sensitivity of MHb neurons

increased chemically-elicited antinociception ( J:280704 )

• mice exhibit enhanced morphine-induced analgesia in thermal (hot plate and tail immersion) and mechanical (Von Frey) pain paradigms, as shown by increases in both maximal response and effect duration across multiple morphine doses

• administration of JNJ-63533054 (a GPR139 agonist) fails to diminish morphine-induced (10mg/kg) analgesia in a dose-dependent manner in the thermal and mechanical pain paradigms, unlike in wild-type control mice

growth/size/body

growth/size/body region phenotype ( J:280704 )

N • at ~4 months of age, mice exhibit normal health, body weight and body composition relative to wild-type controls