Phenotypes Associated with This Genotype

Genotype
MGI:2676450

• Allelic Composition: Irak4^tm1Yeh/Irak4^tm1Yeh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

immune system

decreased B cell proliferation ( J:76098 )

• B lymphocytes show impaired proliferation in response to LPS

abnormal NK cell physiology ( J:76098 )

• interferon gamma production by natural killer cells is undetected after challenge with lymphocytic choriomeningitis virus (LCMV), however cytolytic activity is retained

abnormal macrophage physiology ( J:76098 )

• activated macrophages are unable to produce nitric oxide in responce to IL-1

• macrophages are unable to produce inflammatory mediators in response to treatment with either peptidoglycan or poly(I:C)

• bone-marrow derived macrophages are unresponsive to LPS stimulation and do not produce cytokines

abnormal cytokine level ( J:76098 )

• mutants show no cytokine response to LPS

decreased circulating interferon-gamma level ( J:76098 )

• serum IFN-gamma levels are undetectable after lymphocytic chriomeningitis virus infection

decreased circulating interleukin-1 level ( J:76098 )

• decreased serum IL-1 levels after LPS-induced septic shock

• no response to IL-1 by production of IL-6, Tnf, or nitric oxide, or by activation of Nfkb or Jnk

• responses to Tnf, however, were intact, suggesting that the defect was specific for IL-1

decreased circulating interleukin-6 level ( J:76098 )

• decreased serum IL-6 levels after LPS-induced septic shock or IL-1beta injection

decreased circulating tumor necrosis factor level ( J:76098 )

• decreased serum TNF-alpha levels after LPS-induced septic shock or IL-1beta injection

abnormal cytokine secretion ( J:76098 )

• mutants show no cytokine response to LPS

decreased interleukin-6 secretion ( J:76098 )

• mouse embryonic fibroblasts treated with IL-1 show defects in IL-6 production

• bacterial DNA is unable to stimulate IL-6 production in mutants

decreased tumor necrosis factor secretion ( J:76098 )

• mouse embryonic fibroblasts treated with IL-1 show defects in TNF-alpha production

decreased susceptibility to endotoxin shock ( J:76098 )

• complete resistance to a lethal dose of LPS

increased susceptibility to bacterial infection ( J:76098 )

• whereas 80% of wild-type control mice survived for 10 days after inoculation with Staphylococcus aureus, all inoculated mutant mice die by day 10

homeostasis/metabolism

abnormal cytokine level ( J:76098 )

• mutants show no cytokine response to LPS

decreased circulating interferon-gamma level ( J:76098 )

• serum IFN-gamma levels are undetectable after lymphocytic chriomeningitis virus infection

decreased circulating interleukin-1 level ( J:76098 )

• decreased serum IL-1 levels after LPS-induced septic shock

• no response to IL-1 by production of IL-6, Tnf, or nitric oxide, or by activation of Nfkb or Jnk

• responses to Tnf, however, were intact, suggesting that the defect was specific for IL-1

decreased circulating interleukin-6 level ( J:76098 )

• decreased serum IL-6 levels after LPS-induced septic shock or IL-1beta injection

decreased circulating tumor necrosis factor level ( J:76098 )

• decreased serum TNF-alpha levels after LPS-induced septic shock or IL-1beta injection

hematopoietic system

decreased B cell proliferation ( J:76098 )

• B lymphocytes show impaired proliferation in response to LPS

abnormal NK cell physiology ( J:76098 )

• interferon gamma production by natural killer cells is undetected after challenge with lymphocytic choriomeningitis virus (LCMV), however cytolytic activity is retained

abnormal macrophage physiology ( J:76098 )

• activated macrophages are unable to produce nitric oxide in responce to IL-1

• macrophages are unable to produce inflammatory mediators in response to treatment with either peptidoglycan or poly(I:C)

• bone-marrow derived macrophages are unresponsive to LPS stimulation and do not produce cytokines

cellular

decreased B cell proliferation ( J:76098 )

• B lymphocytes show impaired proliferation in response to LPS