All Phenotypes Yod1<em1Smoc> MGI Mouse

abnormal macrophage physiology ( J:350806 )

• in vitro, isolated bone marrow-derived macrophages (BMDMs) infected with methicillin-resistant Staphylococcus aureus (MRSA) show enhanced NLR-family pyrin domain-containing-3 (NLRP3) inflammasome activation with significantly greater NLRP3 protein levels, Caspase-1 (p20) and IL-1beta (p17) cleavage, apoptosis-associated speck-like protein (ASC) speck formation, and IL-1beta production than MRSA-infected wild-type BMDMs

increased macrophage cytokine production ( J:350806 )

• in vitro, MRSA-infected BMDMs show significantly higher IL-1beta production than similarly infected wild-type BMDMs

• however, IL-6 and TNF secretion is similar to that in wild-type BMDMs after MRSA infection

increased circulating interleukin-1 beta level ( J:350806 )

• MRSA-infected males show significantly higher plasma IL-1beta levels than MRSA-infected wild-type controls

decreased circulating fibrinogen level ( J:350806 )

• at 12 h after i.v. MRSA injection, males show a markedly lower plasma fibrinogen level than MRSA-infected wild-type controls

increased interleukin-1 beta secretion ( J:350806 )

• in vitro, MRSA-infected BMDMs show significantly higher IL-1beta production than similarly infected wild-type BMDMs

increased inflammatory response ( J:350806 )

• after i.v. MRSA injection, males show increased inflammatory cell infiltration in major organs (liver, lung, and kidney) and significantly higher NLRP3 protein levels in liver tissue and plasma IL-1beta levels than MRSA-infected wild-type controls

increased susceptibility to bacterial infection ( J:350806 )

• at 12 h after i.v. injection of MRSA (1 x 10⁸ CFU/mouse), males show a significantly higher bacterial load in blood and major organs (liver, spleen, lung and kidney) as well as higher thrombus and inflammatory cell infiltration in the liver, lung, and kidney than MRSA-infected wild-type controls

• pretreatment with MCC950 (a specific inhibitor of NLRP3 inflammasome) 30 min before MRSA injection significantly improves coagulation and alleviates organ injury

increased susceptibility to bacterial infection induced morbidity/mortality ( J:350806 )

• males show increased susceptibility to MRSA-induced septic death with a significantly lower 14-day survival rate than MRSA-infected wild-type controls

• pretreatment with MCC950 before MRSA injection significantly increases the 14-day survival rate in septic mice

increased circulating D-dimer level ( J:350806 )

• at 12 h after i.v. MRSA injection, males show a markedly higher D-dimer level in blood than MRSA-infected wild-type controls

• pretreatment with MCC950 before MRSA injection significantly reduces plasma levels of D-dimers

increased circulating interleukin-1 beta level ( J:350806 )

• MRSA-infected males show significantly higher plasma IL-1beta levels than MRSA-infected wild-type controls

decreased circulating fibrinogen level ( J:350806 )

• at 12 h after i.v. MRSA injection, males show a markedly lower plasma fibrinogen level than MRSA-infected wild-type controls

abnormal blood coagulation ( J:350806 )

• at 12 h after i.v. MRSA injection, adult males show increased susceptibility to sepsis-induced disseminated intravascular coagulation (DIC), with significantly higher blood levels of thrombin-antithrombin complex (TAT) and plasminogen activator inhibitor 1 (PAI-1) than MRSA-infected wild-type controls

• pretreatment with MCC950 before MRSA injection significantly reduces blood levels of TAT and PAI-1 and improves overall sepsis-induced coagulation

increased partial thromboplastin time ( J:350806 )

• at 12 h after i.v. MRSA injection, males show a markedly higher activated partial thromboplastin time (APTT) than MRSA-infected wild-type controls

• pretreatment with MCC950 before MRSA injection significantly reduces levels of APTT

increased susceptibility to induced thrombosis ( J:350806 )

• after i.v. MRSA injection, males show increased thrombus formation in major organs (liver, lung, and kidney), as determined by H&E staining

• pretreatment with MCC950 before MRSA injection reduces thrombus formation in liver, lung, and kidney

thrombocytopenia ( J:350806 )

• at 12 h after i.v. MRSA injection, males show a markedly lower platelet count than MRSA-infected wild-type controls

• pretreatment with MCC950 before MRSA injection significantly increases the platelet count

abnormal macrophage physiology ( J:350806 )

• in vitro, isolated bone marrow-derived macrophages (BMDMs) infected with methicillin-resistant Staphylococcus aureus (MRSA) show enhanced NLR-family pyrin domain-containing-3 (NLRP3) inflammasome activation with significantly greater NLRP3 protein levels, Caspase-1 (p20) and IL-1beta (p17) cleavage, apoptosis-associated speck-like protein (ASC) speck formation, and IL-1beta production than MRSA-infected wild-type BMDMs

increased macrophage cytokine production ( J:350806 )

• in vitro, MRSA-infected BMDMs show significantly higher IL-1beta production than similarly infected wild-type BMDMs

• however, IL-6 and TNF secretion is similar to that in wild-type BMDMs after MRSA infection

increased susceptibility to bacterial infection induced morbidity/mortality ( J:350806 )

• males show increased susceptibility to MRSA-induced septic death with a significantly lower 14-day survival rate than MRSA-infected wild-type controls

• pretreatment with MCC950 before MRSA injection significantly increases the 14-day survival rate in septic mice

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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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