Phenotypes associated with this allele

• Allele Symbol: Arrb2^tm1Rjl
• Allele Name: targeted mutation 1, Robert J Lefkowitz
• Allele ID: MGI:2157960
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arrb2^tm1Rjl/Arrb2^tm1Rjl	involves: 129X1/SvJ * C57BL/6	MGI:2671985
cx2	Arrb2^tm1Rjl/Arrb2^tm1Rjl Oprm1^tm1Jep/Oprm1^tm1Jep Tg(Th-Oprm1)4Jtw/0	involves: 129S/SvEv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:4355146
cx3	Arrb1^tm1Jse/Arrb1^tm1Jse Arrb2^tm1Rjl/Arrb2^tm1Rjl	involves: 129X1/SvJ * C57BL/6	MGI:4887408

Genotype
MGI:2671985

hm1

• 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

Genotype
MGI:4355146

cx2

• Allelic Composition: Arrb2^tm1Rjl/Arrb2^tm1Rjl; Oprm1^tm1Jep/Oprm1^tm1Jep; Tg(Th-Oprm1)4Jtw/0
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ * C57BL/6 * DBA/2

nervous system

nervous system phenotype ( J:151536 )

N • desensitization and internalization of opioid receptors after met-enkephalin treatment is similar to that in controls

Genotype
MGI:4887408

cx3

• Allelic Composition: Arrb1^tm1Jse/Arrb1^tm1Jse; Arrb2^tm1Rjl/Arrb2^tm1Rjl
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:159121 )

• double homozygotes die within 4 hrs of birth

respiratory system

abnormal lung development ( J:159121 )

• at E18.5, double mutant lungs display impaired prealveoli formation and a thick mesenchyme, indicating a delay in lung development

• mRNA microarray analysis revealed downregulation of a significant proportion of genes involved in various lung morphogenetic processes

decreased mesenchymal cell proliferation involved in lung development ( J:159121 )

• at E18.5, double mutant lungs exhibit a signicant decrease in cell proliferation in the mesenchymal compartment

abnormal lung saccule morphology ( J:159121 )

• at E18.5, peripheral saccules are undilated and lined by a cuboidal epithelium, suggesting pulmonary immaturity

thick lung-associated mesenchyme ( J:159121 )

• at E18.5, double mutant lungs display ia thick mesenchyme

abnormal type I pneumocyte morphology ( J:159121 )

• at E18.5, alveolar type I epithelial cells are missing, as indicated by absence of either AQP-5 or T1a staining in double mutant lungs

abnormal type II pneumocyte morphology ( J:159121 )

• at E18.5, double mutant type II pneumocytes show an abundant amount of cytoplasmic glycogen and lack the typical lamellar bodies normally found in the cytoplasm or in the lumen of peripheral airspaces

• at E18.5, type II cell differentiation is impaired, as indicated by absence of surfactant-associated protein C (SP-C) staining in alveolar epithelial cells

abnormal alveolar lamellar body morphology ( J:159121 )

• disorganized lamellar bodies at E18.5

small lung ( J:159121 )

• at E18.5, double mutant lungs are significantly smaller in size

decreased lung weight ( J:159121 )

• at E18.5, the average ratio of lung weight to wet body weight of double mutants is ~80% of that of wild-type controls

pulmonary hypoplasia ( J:159121 )

• at E18.5, double mutant lungs exhibit a signicant decrease in cell proliferation, in both epithelial and mesenchymal compartments

• however, no significant changes in the extent of apoptosis are observed

atelectasis ( J:159121 )

respiratory distress ( J:159121 )

• double homozygotes exhibit neonatal respiratory distress

decreased surfactant secretion ( J:159121 )

• at E18.5, SP-A and SP-C peptide levels as well as pro-SP-C protein levels are severely reduced

growth/size/body

decreased birth body size ( J:159121 )

• at birth, double homozygous mutant pups are generally smaller than control pups

decreased birth weight ( J:159121 )

• at birth, the average wet body weight of double homozygous mutant pups is ~60% of that of wild-type pups

decreased fetal weight ( J:159121 )

• at E18.5, the average wet body weight of double homozygous mutant fetuses is only ~60% of that of wild-type fetuses

behavior/neurological

no spontaneous movement ( J:159121 )

• at birth, double homozygous mutant pups lack spontaneous movement

homeostasis/metabolism

cyanosis ( J:159121 )

• at birth, double homozygous mutant pups appear cyanotic

cellular

decreased mesenchymal cell proliferation involved in lung development ( J:159121 )

• at E18.5, double mutant lungs exhibit a signicant decrease in cell proliferation in the mesenchymal compartment