Phenotypes Associated with This Genotype

Genotype
MGI:2671985

• Allelic Composition: Arrb2^tm1Rjl/Arrb2^tm1Rjl
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

immune system

abnormal lymphocyte physiology ( J:76872 )

• chemotaxic response of both T and B lymphocytes to CXCL12 is significantly reduced

increased circulating interleukin-6 level ( J:112607 )

• there is a 2-fold increase in serum levels of IL-6 in mutant mice after LPS injection compared to wild-type controls

abnormal circulating tumor necrosis factor level ( J:112607 )

• there is a 3-fold increase in serum levels of TNF 1 hour after injection with LPS compared wild-type controls

increased interleukin-12b secretion ( J:112607 )

• bone marrow derived macrophages produce 1.5-fold to 2-fold more IL12p40 in response to agonists to TLR-3, -4, -9, and CD40 compared to controls

increased interleukin-6 secretion ( J:112607 )

• there is a 2-fold increase in serum levels of IL-6 in mutant mice compared to wild-type controls

increased tumor necrosis factor secretion ( J:112607 )

• bone marrow derived macrophages produce 1.5-fold to 3-fold more TNF in response to agonists to TLR-3, -4, -9, and CD40 compared to controls

increased acute inflammation ( J:112607 )

• mice have a heightened response to endotoxins including less survivability and increased pro-inflammatory cytokine production

increased susceptibility to endotoxin shock ( J:112607 )

• 89% of mice die within 12 hours of a LPS and D-galactosamine injection compared to 0% for wild-type mice

• the mice die of endotoxin shock

homeostasis/metabolism

increased circulating interleukin-6 level ( J:112607 )

• there is a 2-fold increase in serum levels of IL-6 in mutant mice after LPS injection compared to wild-type controls

abnormal circulating tumor necrosis factor level ( J:112607 )

• there is a 3-fold increase in serum levels of TNF 1 hour after injection with LPS compared wild-type controls

abnormal body temperature homeostasis ( J:59162 )

• homozygotes exhibit no significant differences in basal body temperature relative to wild-type mice (36.8 0.1C vs 36.4 0.1C, respectively)

• however, homozygotes display a significantly increased and prolonged hypothermia in response to morphine treatment

behavior/neurological

increased chemically-elicited antinociception ( J:59162 )

• homozygotes are viable and overtly normal with no significant differences in morphine metabolism or basal responses to the hot plate test relative to wild-type mice

• however, homozygotes exhibit enhanced and prolonged morphine-induced antinociception, as measured by hot-plate response latencies (56C), with significant analgesia noted at 4 hrs [% maximum possible effect = 31 0.4%] after s.c. morphine injection relative to wild-type mice in which analgesia of the same morphine dose (10 mg/kg) wanes after ~90 min

• enhanced morphine-induced antinociception is dose-dependent and completely reversed with the mu opioid receptor (OR) antagonist naloxone (2.5 mg/kg sc), suggesting impaired OR desensitization

• in addition, antinociceptive behaviors are correlated with enhanced OR-G-protein coupling in mutant hypothalamus, brainstem, periaqueductal gray tissues

hematopoietic system

abnormal lymphocyte physiology ( J:76872 )

• chemotaxic response of both T and B lymphocytes to CXCL12 is significantly reduced