Mouse Genome Informatics
ht
    Nlrp3tm1Wstr/Nlrp3+
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• some mice die before weaning

growth/size
• mice have decreased linear growth compared to controls
• mice have decreased weight gain compared to controls

reproductive system
• few mice that survive into adulthood are able to have offspring

immune system
• the percentage of Th17 cells isolated from inflamed mice is greatly increased
• transcription factor analysis suggests majority of T cells in inflamed mice are of the Th17 phenotype
• the percentage of IFN-gamma producing T cells found in inflamed animals is increased compared to controls
• white blood cell count is elevated in mice with dermatitis
• CD4+ T cells isolated from mice suffering dermatitis have an activated phenotype (CD25hi CD69hi CD44hi and CD62Llo)
• red pulp areas are filled with neutrophils and islands of trilineage hematopoietic cells
• mice suffering from dermatitis have enlarged spleens that contain increased numbers of neutrophils
• splenic and bone marrow derived macrophages secrete large amounts of IL-1beta and IL-18 upon stimulation through TLR receptors in the absence of exogenous ATP
• lymph nodes show loss of germinal center architecture, poorly developed follicles, expanded interfollicular regions, and a diffuse neutrophil infiltration
• mice have enlarged cervical, axillary, and inguinal nodes that drain areas of dermatitis containing high numbers of neutrophils
• bone marrow derived dendritic cells secrete large amounts of IL-1beta and IL-18 upon stimulation through TLR receptors in the absence of exogenous ATP
• mutant dendritic cells mediate differentiation of higher number of T cells into the Th17 phenotype in vitro, an effect partly attributable to IL-1beta secretion
• young mice (i.e. prior to development of dermatitis) show greater DTH responses than controls
• response is characterized by greater ear swelling, thickening of epidermis and dermis, as well as heavier tissue infiltration of neutrophils and monocytes
• macrophages and dendritic cells secrete large amounts of IL-1beta upon stimulation through TLR receptors in the absence of exogenous ATP
• the large increase in Th17 cells leads to increased IL-17 secretion
• macrophages and dendritic cells secrete large amounts of IL-18 upon stimulation through TLR receptors in the absence of exogenous ATP
• anti-dsDNA antibodies are elevated in mice regardless if they are suffering from dermatitis or not
• as mice get older the develop chronic inflammation characterized by dermatitis and leukocyte infiltration of numerous tissues
• affecting the ears, top of the head, and the tail base areas of mice at 8 to 16 weeks of age
• the skin has marked thickening and heavy neutrophil infiltration in both epidermis and dermis

liver/biliary system
• mice suffering from dermatitis have enlarged livers with leukocyte infiltration

hematopoietic system
• the percentage of Th17 cells isolated from inflamed mice is greatly increased
• transcription factor analysis suggests majority of T cells in inflamed mice are of the Th17 phenotype
• the percentage of IFN-gamma producing T cells found in inflamed animals is increased compared to controls
• white blood cell count is elevated in mice with dermatitis
• CD4+ T cells isolated from mice suffering dermatitis have an activated phenotype (CD25hi CD69hi CD44hi and CD62Llo)
• red pulp areas are filled with neutrophils and islands of trilineage hematopoietic cells
• mice suffering from dermatitis have enlarged spleens that contain increased numbers of neutrophils
• splenic and bone marrow derived macrophages secrete large amounts of IL-1beta and IL-18 upon stimulation through TLR receptors in the absence of exogenous ATP
• and bone marrow derived macrophages secrete large amounts of IL-1beta and IL-18 upon stimulation through TLR receptors in the absence of exogenous ATP

integument
• affecting the ears, top of the head, and the tail base areas of mice at 8 to 16 weeks of age
• the skin has marked thickening and heavy neutrophil infiltration in both epidermis and dermis

Mouse Models of Human Disease
OMIM IDRef(s)
Muckle-Wells Syndrome; MWS 191900 J:150053