All Phenotypes Ccr4<tm1Pwr> MGI Mouse

N

• in vitro, homozygotes display normal Th2 and Th1 cell differentiation relative to wild-type mice

• in an OVA-induced model of airway inflammation, homozygotes display normal Th2-associated bronchial hyperreactivity in response to inhaled methacholine after OVA priming and intranasal challenge with saline, with no differences in OVA-induced eosinophilia in BALF and lung tissue, in total cell count or individual leukocyte populations in BALF, or in OVA-specific Ig titers relative to wild-type mice

decreased eosinophil cell number ( J:120221 )

• after A. fumigatus infection in the bronchoalveolar lavage

increased neutrophil cell number ( J:120221 )

• after A. fumigatus infection in the bronchoalveolar lavage

decreased lymphocyte cell number ( J:70088 )

• at 24 hrs after high dose LPS treatment, homozygotes show a reduction in the number of lymphocytes in the peritoneal lavage relative to wild-type mice

decreased macrophage cell number ( J:70088 )

• at 24 hrs after high dose LPS treatment, homozygotes display significantly fewer macrophages in the peritoneal lavage, with reduced numbers of CD11b⁺ and CD14⁺ cells and an absence or severely reduced number of F4/80-expressing cells relative to wild-type mice

increased macrophage cell number ( J:120221 )

• after A. fumigatus infection in the bronchoalveolar lavage

decreased IgE level ( J:120221 )

• 30 days after A. fumigatus infection

increased IgE level ( J:120221 )

• 3 and 7 days after A. fumigatus infection

increased IgG1 level ( J:120221 )

• 3 days after A. fumigatus infection

abnormal splenocyte physiology ( J:70088 )

• unexpectedly, mutant splenocytes show no chemotactic response to human or mouse chemokine (C-C motif) ligand 3 (also known as macrophage inflammatory protein MIP-1alpha)

• in contrast, the response of mutant splenocytes to human RANTES is similar to that observed in wild-type mice

abnormal cytokine secretion ( J:120221 )

abnormal chemokine secretion ( J:70088 )

• at 3 hrs after injection of a high dose of LPS (60 mg/kg), homozygotes show a significant decrease in serum MIP-alpha levels relative to wild-type mice, suggesting a possible macrophage defect

increased interferon-gamma secretion ( J:120221 )

• 3 days after A. fumigatus infection

decreased interleukin-1 beta secretion ( J:70088 )

• at 3 hrs after injection of a high dose of LPS (60 mg/kg), homozygotes show a 6-fold decrease in serum IL-1beta levels relative to wild-type mice

• in contrast, IL-6 production remains unchanged relative to wild-type mice

decreased interleukin-10 secretion ( J:120221 )

• 30 days after A. fumigatus infection

increased interleukin-10 secretion ( J:120221 )

• 3 days after A. fumigatus infection

decreased interleukin-13 secretion ( J:120221 )

• 30 days after A. fumigatus infection

decreased interleukin-4 secretion ( J:120221 )

• 30 days after A. fumigatus infection

increased interleukin-4 secretion ( J:120221 )

• 3 days after A. fumigatus infection

decreased interleukin-5 secretion ( J:120221 )

• 30 days after A. fumigatus infection

increased interleukin-5 secretion ( J:120221 )

• 3 days after A. fumigatus infection

decreased tumor necrosis factor secretion ( J:70088 )

• in response to a high LPS dose (60 mg/kg), homozygotes fail to induce significant levels of serum TNF, whereas wild-type mice show a sharp increase in serum TNF levels at 1.5 hrs which return to baseline by 4 hrs after LPS treatment

• in vitro, peritoneal lavage cells from naive homozygotes produce significantly lower TNF levels when cultured for 18 hrs in the presence of 1 g/ml LPS relative to cells from naive wild-type mice (107 11 versus 201 18 pg/ml, respectively)

increased tumor necrosis factor secretion ( J:120221 )

• after A. fumigatus infection

decreased susceptibility to endotoxin shock ( J:70088 )

• in response to high doses of LPS (60-120 mg/kg), homozygotes show no differences in initial platelet mobilization but display milder signs of shivering and lethargy than wild-type during the first few hours after LPS injection, with platelet counts returning to normal at day 5 and 93% of homozygotes still alive on day 6, whereas all wild-type die between 2 and 4 days after treatment

• in response to a low dose of LPS (1 g) plus 8 mg of D-gal, 9 of 12 homozygotes survive whereas the majority of wild-type (11 of 12) die; following treatment with 4 g of LPS plus D-gal, all homozygotes tested die with a 6-hr delay relative to wild-type mice

decreased susceptibility to fungal infection ( J:120221 )

• 7 days after Aspergillus fumigatus infection, mice clear fungal spores from the lungs; increased neutrophil, eosinophil, and macrophage numbers in the bronchoalveolar lavage (BAL); increased early airway resistance; increased early levels of TNFalpha, IFN-gamma, IL4, IL5, and IL10 in the BAL; and increased early IgE and IgG1 levels compared with wild-type mice

• 3 days after A. fumigatus infection airway resistance is increased compared to in wild-type mice

• 30 days after A. fumigatus infection airway resistance is decreased compared to in wild-type mice

decreased airway resistance ( J:120221 )

• 30 days after A. fumigatus infection

increased airway resistance ( J:120221 )

• 3 days after A. fumigatus infection

decreased eosinophil cell number ( J:120221 )

• after A. fumigatus infection in the bronchoalveolar lavage

increased neutrophil cell number ( J:120221 )

• after A. fumigatus infection in the bronchoalveolar lavage

decreased lymphocyte cell number ( J:70088 )

• at 24 hrs after high dose LPS treatment, homozygotes show a reduction in the number of lymphocytes in the peritoneal lavage relative to wild-type mice

decreased macrophage cell number ( J:70088 )

• at 24 hrs after high dose LPS treatment, homozygotes display significantly fewer macrophages in the peritoneal lavage, with reduced numbers of CD11b⁺ and CD14⁺ cells and an absence or severely reduced number of F4/80-expressing cells relative to wild-type mice

increased macrophage cell number ( J:120221 )

• after A. fumigatus infection in the bronchoalveolar lavage

decreased IgE level ( J:120221 )

• 30 days after A. fumigatus infection

increased IgE level ( J:120221 )

• 3 and 7 days after A. fumigatus infection

increased IgG1 level ( J:120221 )

• 3 days after A. fumigatus infection

abnormal splenocyte physiology ( J:70088 )

• unexpectedly, mutant splenocytes show no chemotactic response to human or mouse chemokine (C-C motif) ligand 3 (also known as macrophage inflammatory protein MIP-1alpha)

• in contrast, the response of mutant splenocytes to human RANTES is similar to that observed in wild-type mice

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

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

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