Phenotypes Associated with This Genotype

Genotype
MGI:3605004

• Allelic Composition: Il6^tm1Poli/Il6^tm1Poli
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:48865 , J:37026 )

• in contrast, male and female homozygotes show no significant changes in survival relative to wild-type counterparts during CLP-induced sepsis (J:48865)

• at 24 hrs or longer after partial hepatectomy, homozygotes exhibit significantly increased mortality and morbidity (40%) relative to wild-type (10%) or IL-6-treated homozygotes (8%) (J:37026)

liver/biliary system

abnormal liver morphology ( J:37026 )

• homozygotes exhibit normal liver architecture prior to partial (70%) hepatectomy

• however, at 4 to 5 days after 70% hepatectomy, livers of jaundiced homozygotes appear small and erythematous with extensive areas of necrosis

hepatic necrosis ( J:37026 )

• at 36 to 72 hrs after partial hepatectomy, livers of most homozygotes show massive hepatic necrosis and ballooning degeneration of hepatocytes, in the absence of apoptosis

• little or no necrosis is observed in the livers of the 50% of homozygotes that survive 96 and 120 hrs after hepatectomy

impaired liver regeneration ( J:37026 )

• after partial hepatectomy, homozygotes display impaired liver regeneration typified by liver necrosis and failure

• hepatectomized homozygotes show decreased levels of induced hepatocyte DNA synthesis, with 20-25% of wild-type levels at 36 hrs and >48 hours after surgery

• treatment with a single preoperative dose of IL-6 restores hepatocyte proliferation to nearly wild-type levels and prevents liver damage

liver failure ( J:37026 )

• between 24 and 96 hrs after partial hepatectomy, ~28% of homozygotes exhibit lethargy, anorexia, and tremulousness, some with gross jaundice

• in contrast, no hepatic necrosis or signs of liver failure are noted in hepatectomized wild-type or IL-6-treated homozygotes at any time after hepatectomy

homeostasis/metabolism

impaired febrile response ( J:48865 )

• during sepsis induced by cecal ligation and puncture (CLP), male homozygotes maintain a profound hypothermia but fail exhibit subsequent fever

decreased susceptibility to injury ( J:68063 )

• homozygotes subjected to resuscitated HS exhibit less lung injury, (i.e. reduced pneumocyte swelling, interstitial edema, and cellular infiltration) relative to sham controls

• in addition, homozygotes subjected to resuscitated HS fail to exhibit significant focal liver necrosis relative to sham controls

growth/size/body

growth/size/body region phenotype ( J:48865 )

N • male homozygotes show a normal cachectic response during sepsis induced by cecal ligation and puncture (CLP)

behavior/neurological

abnormal food intake ( J:48865 )

• male homozygotes display prolonged anorexia during sepsis

immune system

impaired neutrophil recruitment ( J:68063 )

• homozygotes subjected to resuscitated hemorrhagic shock (HS) fail to exhibit significant infiltration of PMN into the lung interstitium and alveoli relative to sham controls

• in addition, homozygotes subjected to resuscitated HS fail to exhibit significant liver PMN infiltration relative to sham controls

decreased inflammatory response ( J:68063 )

• homozygotes subjected to resuscitated HS fail to exhibit features of postresuscitation inflammation, concomittant with impaired liver STAT3 and NF-kappaB activation

hematopoietic system

impaired neutrophil recruitment ( J:68063 )

• homozygotes subjected to resuscitated hemorrhagic shock (HS) fail to exhibit significant infiltration of PMN into the lung interstitium and alveoli relative to sham controls

• in addition, homozygotes subjected to resuscitated HS fail to exhibit significant liver PMN infiltration relative to sham controls