Mouse Genome Informatics
cn1
    Il1r1tm1Roml/Il1r1tm1Roml
Nlrp3tm1Hhf/Nlrp3+
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• postnatal lethality does not occur to mice on a IL-1 receptor null background (J:150054)

immune system
• variable skin inflammation is observed

integument
• variable skin inflammation is observed


Mouse Genome Informatics
cn2
    Nlrp3tm1Hhf/Nlrp3+
Pycardtm1Flv/Pycardtm1Flv
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice appear phenotypically normal and do not develop the inflammatory disease that conditional heterozygotes develop on an intact Pycard background


Mouse Genome Informatics
cn3
    Nlrp3tm1Flv/Nlrp3tm1Hhf
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 2 and 14 days after birth probably due to multisystem organ failure secondary to inflammation and necrosis
• genotype demonstrates inflammatory disease of the conditional allele does not require presence of wild-type allele

immune system
• mice have pronounced leukocytic infiltrates in skin, liver, spleen, joint, sinus, conjunctiva, bone marrow, and tongue that are mainly neutrophilic

Mouse Models of Human Disease
OMIM IDRef(s)
Muckle-Wells Syndrome; MWS 191900 J:150054


Mouse Genome Informatics
cn4
    Nlrp3tm1Hhf/Nlrp3+
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 2 and 14 days after birth probably due to multisystem organ failure secondary to inflammation and necrosis
• 70% of mice die between 7-14 days

growth/size/body
• mutant pups gained weight slowly, and then lost weight before dying

digestive/alimentary system
• substantial necrosis occurs in the gut that is not associated with inflammation

renal/urinary system
• substantial necrosis occurs in the kidney that is not associated with inflammation

immune system
• white blood cell count is mildly elevated
• pronounced neutrophilia is evident in these mice
• GCSF is elevated in the sera of 6-8 day old mice
• CXCL1 levels are elevated in the sera of mice 6-8 days old
• IL-1beta levels in the sera of 6-8 day old mice are elevated 3-fold
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
• IL-18 levels are elevated in the sera of 6-8 day old mice
• IL-6 levels are elevated in the sera of 6-8 day old mice
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
• TNF levels in the sera of 6-8 day old mice are elevated
• mice have pronounced leukocytic infiltrates in skin, liver, spleen, joint, sinus, conjunctiva, bone marrow, and tongue that are mainly neutrophilic

homeostasis/metabolism
• GCSF is elevated in the sera of 6-8 day old mice
• CXCL1 levels are elevated in the sera of mice 6-8 days old
• IL-1beta levels in the sera of 6-8 day old mice are elevated 3-fold
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
• IL-18 levels are elevated in the sera of 6-8 day old mice
• IL-6 levels are elevated in the sera of 6-8 day old mice
• levels of this cytokine are also elevated in the dermis and epidermis, which may contribute to the skin pathology
• TNF levels in the sera of 6-8 day old mice are elevated

hematopoietic system
• white blood cell count is mildly elevated
• pronounced neutrophilia is evident in these mice
• thrombocytosis is evident in these mice

integument
• hair growth does not occur in these mice
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4

Mouse Models of Human Disease
OMIM IDRef(s)
Muckle-Wells Syndrome; MWS 191900 J:150054


Mouse Genome Informatics
cn5
    Nlrp3tm1Hhf/Nlrp3+
Rag1tm1Mom/Rag1tm1Mom
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 2 and 14 days after birth probably due to multisystem organ failure secondary to inflammation and necrosis
• 70% of mice die between 7-14 days
• absence of B and T cells demonstrates disease is not caused by the adaptive immune system

growth/size/body
• mutant pups gained weight slowly, and then lost weight before dying

immune system

hematopoietic system

integument
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4


Mouse Genome Informatics
cn6
    Nlrp3tm1Hhf/Nlrp3+
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro
• bone marrow derived dendritic cells hypersecrete the mature form of IL-1beta in response to activation
• the maximal response is 300-fold greater than controls
• DCs are able to secrete IL1-beta without the presence of exogenous ATP
• mutant DCs cells have an enhanced ability to stimulate T cells to differentiate into a Th17 subtypes when presenting cognate antigen
• mutant DCs also enhance Th1 and Th2 differentation when co-cultured with T cells in the presence of polarizing cytokines

hematopoietic system
• peritoneal macrophages are able to secrete IL-1beta in the absence of ATP when activated in vitro

Mouse Models of Human Disease
OMIM IDRef(s)
Muckle-Wells Syndrome; MWS 191900 J:150054


Mouse Genome Informatics
cn7
    Nlrp3tm1Hhf/Nlrp3+
Tg(Zp3-cre)3Mrt/?

involves: 129/Sv * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die between 2 and 14 days after birth probably due to multisystem organ failure secondary to inflammation and necrosis

growth/size/body
• mutant pups gained weight slowly, and then lost weight before dying

immune system
• white blood cell count is mildly elevated
• pronounced neutrophilia is evident in these mice
• mice have pronounced leukocytic infiltrates in skin, liver, spleen, joint, sinus, conjunctiva, bone marrow, and tongue that are mainly neutrophilic

digestive/alimentary system
• substantial necrosis occurs in the gut that is not associated with inflammation

renal/urinary system
• substantial necrosis occurs in the kidney that is not associated with inflammation

hematopoietic system
• white blood cell count is mildly elevated
• pronounced neutrophilia is evident in these mice
• thrombocytosis is evident in these mice

integument
• hair growth does not occur in these mice
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4
• 1-2 day old mice have skin abscesses that develop into erythema and scaly skin by day 4

Mouse Models of Human Disease
OMIM IDRef(s)
Muckle-Wells Syndrome; MWS 191900 J:150054


Mouse Genome Informatics
cx8
    Nlrp3tm1Hhf/Nlrp3+
Tg(CAG-cre/Esr1*)5Amc/?

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• some older mice have slower weight gain

immune system
• some older mice develop skin inflammation suggesting leaky expression of the cre recombinase

integument
• some older mice develop skin inflammation suggesting leaky expression of the cre recombinase