Phenotypes associated with this allele

• Allele Symbol: Nlrp3⁺
• Allele Name: wild type
• Allele ID: MGI:2653834
• Summary: 18 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Nlrp3^M10Btlr/Nlrp3^+	C57BL/6J-Nlrp3^M10Btlr	MGI:5789650
ht2	Nlrp3^m5Btlr/Nlrp3^+	C57BL/6J-Nlrp3^m5Btlr	MGI:5466149
ht3	Nlrp3^M6Btlr/Nlrp3^+	C57BL/6J-Nlrp3^M6Btlr	MGI:5607729
ht4	Nlrp3^M7Btlr/Nlrp3^+	C57BL/6J-Nlrp3^M7Btlr	MGI:5608884
ht5	Nlrp3^M8Btlr/Nlrp3^+	C57BL/6J-Nlrp3^M8Btlr	MGI:5613605
ht6	Nlrp3^M9Btlr/Nlrp3^+	C57BL/6J-Nlrp3^M9Btlr	MGI:5632192
ht7	Nlrp3^tm3.1Hhf/Nlrp3^+	involves: 129	MGI:5517789
ht8	Nlrp3^tm1Wstr/Nlrp3^+	involves: C57BL/6	MGI:3850080
cn9	Nlrp3^tm1Hhf/Nlrp3^+ Pycard^tm1Flv/Pycard^tm1Flv Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129 * C57BL/6	MGI:3850058
cn10	Il1r1^tm1Roml/Il1r1^tm1Roml Nlrp3^tm1Hhf/Nlrp3^+ Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129 * C57BL/6	MGI:3850053
cn11	Nlrp3^tm2Hhf/Nlrp3^+ Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:3850048
cn12	Nlrp3^tm1Hhf/Nlrp3^+ Rag1^tm1Mom/Rag1^tm1Mom Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:3850056
cn13	Nlrp3^tm1Hhf/Nlrp3^+ Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:3850045
cn14	Nlrp3^tm2Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850052
cn15	Nlrp3^tm1Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850050
cn16	Nlrp3^tm1Hhf/Nlrp3^+ Tg(Zp3-cre)3Mrt/?	involves: 129/Sv * FVB/N	MGI:3850044
cx17	Nlrp3^tm2Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850051
cx18	Nlrp3^tm1Hhf/Nlrp3^+ Tg(CAG-cre/Esr1*)5Amc/?	involves: 129/Sv * C57BL/6 * CBA	MGI:3850049

Genotype
MGI:5789650

ht1

• Allelic Composition: Nlrp3^M10Btlr/Nlrp3⁺
• Genetic Background: C57BL/6J-Nlrp3^M10Btlr

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

immune system

decreased interleukin-1 beta secretion ( J:234254 )

• mice showed some decrease in secretion of the proinflammatory cytokine interleukin (IL)-1beta in response to priming with lipopolysaccharide (LPS) followed by nigericin treatment

Genotype
MGI:5466149

ht2

• Allelic Composition: Nlrp3^m5Btlr/Nlrp3⁺
• Genetic Background: C57BL/6J-Nlrp3^m5Btlr

immune system

decreased interleukin-1 beta secretion ( J:192651 )

• in response to priming with lipopolysaccharide (LPS) followed by nigericin treatment

Genotype
MGI:5607729

ht3

• Allelic Composition: Nlrp3^M6Btlr/Nlrp3⁺
• Genetic Background: C57BL/6J-Nlrp3^M6Btlr

immune system

decreased interleukin-1 beta secretion ( J:216047 )

• mice bearing this mutation exhibit attenuated inflammatory responses related to decreased secretion of the proinflammatory cytokine interleukin- (IL-) 1 beta in response to priming with lipopolysaccharide (LPS) followed by nigericin treatment.

Genotype
MGI:5608884

ht4

• Allelic Composition: Nlrp3^M7Btlr/Nlrp3⁺
• Genetic Background: C57BL/6J-Nlrp3^M7Btlr

immune system

abnormal macrophage cytokine production ( J:216048 )

• thioglycolate-elicited peritoneal macrophages from mice bearing this mutation secrete less interleukin-1 beta than do cells of control mice in response to priming with bacterial lipopolysaccharide (LPS) followed by nigericin treatment; IL-1 beta secretion by heterozygous mutant macrophages is intermediate between homozygous and wild-type levels.

decreased interleukin-1 beta secretion ( J:216048 )

• thioglycolate-elicited peritoneal macrophages from mice bearing this mutation secrete less interleukin-1 beta than do cells of control mice in response to priming with bacterial lipopolysaccharide (LPS) followed by nigericin treatment; IL-1 beta secretion by heterozygous mutant macrophages is intermediate between homozygous and wild-type levels.

hematopoietic system

abnormal macrophage cytokine production ( J:216048 )

• thioglycolate-elicited peritoneal macrophages from mice bearing this mutation secrete less interleukin-1 beta than do cells of control mice in response to priming with bacterial lipopolysaccharide (LPS) followed by nigericin treatment; IL-1 beta secretion by heterozygous mutant macrophages is intermediate between homozygous and wild-type levels.

Genotype
MGI:5613605

ht5

• Allelic Composition: Nlrp3^M8Btlr/Nlrp3⁺
• Genetic Background: C57BL/6J-Nlrp3^M8Btlr

immune system

decreased interleukin-1 beta secretion ( J:217294 )

• in response to priming with lipopolysaccharide (LPS) followed by nigericin treatment

Genotype
MGI:5632192

ht6

• Allelic Composition: Nlrp3^M9Btlr/Nlrp3⁺
• Genetic Background: C57BL/6J-Nlrp3^M9Btlr

immune system

decreased interleukin-1 beta secretion ( J:220071 )

• decreased secretion of the proinflammatory cytokine interleukin (IL)-1beta in response to priming with lipopolysaccharide (LPS) followed by nigericin treatment; heterozygous mutants exhibit a slightly intermediate phenotype compared to homozygous and wild-type mice, but the mutation was mapped as dominantly inherited.

Genotype
MGI:5517789

ht7

• Allelic Composition: Nlrp3^tm3.1Hhf/Nlrp3⁺
• Genetic Background: involves: 129

Nlrp3^tm3.1Hhf/Nlrp3⁺ mice display joint inflammation

mortality/aging

postnatal lethality, complete penetrance ( J:202147 )

• mice usually die by 2 to 3 weeks of age

skeleton

increased osteoclast cell number ( J:202147 )

joint inflammation ( J:202147 )

osteomyelitis ( J:202147 )

• resulting in increased bone resorption

decreased femur size ( J:202147 )

• decreased femur size

abnormal bone marrow cavity morphology ( J:202147 )

• increased relative to small bone size

decreased bone mineral density ( J:202147 )

• whole body as well as cortical and trabecular compartments of the axial and appendicular skeleton

decreased compact bone area ( J:202147 )

decreased compact bone thickness ( J:202147 )

abnormal trabecular bone morphology ( J:202147 )

• increased trabecular in the region continguous to the spike but not the region that contains this structure

decreased bone trabecula number ( J:202147 )

• in the region continguous to the spike but not the region that contains this structure

decreased trabecular bone thickness ( J:202147 )

• in the region continguous to the spike but not the region that contains this structure

decreased bone mass ( J:202147 )

decreased trabecular bone mass ( J:202147 )

• in the region continuous to the spike area

decreased chondrocyte number ( J:202147 )

• in the central zone of the epiphysis, as determined by collagen staining

abnormal skeleton development ( J:202147 )

• stunted skeletal growth

• small skeleton at P13

abnormal osteoclast differentiation ( J:202147 )

• higher osteoclast formation potential in the bone marrow

abnormal long bone hypertrophic chondrocyte zone ( J:202147 )

• reduced thickness

decreased width of hypertrophic chondrocyte zone ( J:202147 )

• especially in the mid region

disorganized long bone epiphyseal plate ( J:202147 )

• with tissue spikes that extend into the primary spongiosa of the distal femur

abnormal long bone epiphysis morphology ( J:202147 )

• acellular central structure in the epiphysis of the distal femur and proximal tibia

increased bone resorption ( J:202147 )

• due to inflammation

abnormal chondrocyte physiology ( J:202147 )

• increased apoptosis particularly in the area surrounding the spike

immune system

immune system phenotype ( J:202147 )

N • mice exhibit normal serum levels of IL1a, IL2, IL10 and IL17

abnormal osteoclast differentiation ( J:202147 )

• higher osteoclast formation potential in the bone marrow

increased granulocyte number ( J:202147 )

• in various tissues, including joints and meninges

increased neutrophil cell number ( J:202147 )

• circulating and in the bone marrow

decreased lymphocyte cell number ( J:202147 )

• severe

increased lymphocyte cell number ( J:202147 )

• neutrophilic in the periphery

increased osteoclast cell number ( J:202147 )

increased monocyte cell number ( J:202147 )

• inflammatory monocytes in the bone marrow

abnormal circulating chemokine level ( J:202147 )

• increased serum chemokine (eotaxin, KC, MCP-1, MIP-1a, MIP-1b and RANTES) levels

increased circulating interleukin-1 beta level ( J:202147 )

decreased circulating interleukin-12b level ( J:202147 )

increased circulating interleukin-13 level ( J:202147 )

increased circulating interleukin-18 level ( J:202147 )

increased circulating interleukin-3 level ( J:202147 )

increased circulating interleukin-4 level ( J:202147 )

decreased circulating interleukin-5 level ( J:202147 )

increased circulating interleukin-6 level ( J:202147 )

increased circulating interleukin-9 level ( J:202147 )

increased circulating tumor necrosis factor level ( J:202147 )

increased interferon-gamma secretion ( J:202147 )

increased interleukin-1 beta secretion ( J:202147 )

• 3-fold in the bone marrow

increased inflammatory response ( J:202147 )

• systemic inflammation

meningitis ( J:202147 )

joint inflammation ( J:202147 )

osteomyelitis ( J:202147 )

• resulting in increased bone resorption

growth/size/body

decreased body weight ( J:202147 )

• by P5

postnatal growth retardation ( J:202147 )

• by P5

cellular

abnormal osteoclast differentiation ( J:202147 )

• higher osteoclast formation potential in the bone marrow

decreased cell proliferation ( J:202147 )

• of bone marrow cells

nervous system

meningitis ( J:202147 )

homeostasis/metabolism

abnormal circulating chemokine level ( J:202147 )

• increased serum chemokine (eotaxin, KC, MCP-1, MIP-1a, MIP-1b and RANTES) levels

increased circulating interleukin-1 beta level ( J:202147 )

decreased circulating interleukin-12b level ( J:202147 )

increased circulating interleukin-13 level ( J:202147 )

increased circulating interleukin-18 level ( J:202147 )

increased circulating interleukin-3 level ( J:202147 )

increased circulating interleukin-4 level ( J:202147 )

decreased circulating interleukin-5 level ( J:202147 )

increased circulating interleukin-6 level ( J:202147 )

increased circulating interleukin-9 level ( J:202147 )

increased circulating tumor necrosis factor level ( J:202147 )

hematopoietic system

abnormal osteoclast differentiation ( J:202147 )

• higher osteoclast formation potential in the bone marrow

anemia ( J:202147 )

decreased erythrocyte cell number ( J:202147 )

increased granulocyte number ( J:202147 )

• in various tissues, including joints and meninges

increased neutrophil cell number ( J:202147 )

• circulating and in the bone marrow

thrombocytosis ( J:202147 )

decreased lymphocyte cell number ( J:202147 )

• severe

increased lymphocyte cell number ( J:202147 )

• neutrophilic in the periphery

increased osteoclast cell number ( J:202147 )

increased monocyte cell number ( J:202147 )

• inflammatory monocytes in the bone marrow

abnormal bone marrow cell physiology ( J:202147 )

• decreased proliferation and survival

limbs/digits/tail

decreased femur size ( J:202147 )

• decreased femur size

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CINCA Syndrome		DOID:0090029	OMIM:607115	J:202147

Genotype
MGI:3850080

ht8

• Allelic Composition: Nlrp3^tm1Wstr/Nlrp3⁺
• Genetic Background: involves: C57BL/6

mortality/aging

decreased survivor rate ( J:150053 )

• some mice die before weaning

growth/size/body

postnatal growth retardation ( J:150053 )

• mice have decreased linear growth compared to controls

slow postnatal weight gain ( J:150053 )

• mice have decreased weight gain compared to controls

enlarged liver ( J:150053 )

• mice suffering from dermatitis have enlarged livers with leukocyte infiltration

enlarged spleen ( J:150053 )

• mice suffering from dermatitis have enlarged spleens that contain increased numbers of neutrophils

reproductive system

reduced fertility ( J:150053 )

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

immune system

enlarged spleen ( J:150053 )

• mice suffering from dermatitis have enlarged spleens that contain increased numbers of neutrophils

abnormal CD4-positive, alpha-beta T cell number ( J:150053 )

• 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

increased T-helper 1 cell number ( J:150053 )

• the percentage of IFN-gamma producing T cells found in inflamed animals is increased compared to controls

increased leukocyte cell number ( J:150053 )

• white blood cell count is elevated in mice with dermatitis

increased activated T cell number ( J:150053 )

• CD4⁺ T cells isolated from mice suffering dermatitis have an activated phenotype (CD25^hi CD69^hi CD44^hi and CD62L^lo)

abnormal spleen red pulp morphology ( J:150053 )

• red pulp areas are filled with neutrophils and islands of trilineage hematopoietic cells

abnormal macrophage physiology ( J:150053 )

• 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

abnormal lymph node morphology ( J:150053 )

• lymph nodes show loss of germinal center architecture, poorly developed follicles, expanded interfollicular regions, and a diffuse neutrophil infiltration

enlarged lymph nodes ( J:150053 )

• mice have enlarged cervical, axillary, and inguinal nodes that drain areas of dermatitis containing high numbers of neutrophils

abnormal dendritic cell physiology ( J:150053 )

• 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

increased susceptibility to type IV hypersensitivity reaction ( J:150053 )

• 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

increased interleukin-1 beta secretion ( J:150053 )

• macrophages and dendritic cells secrete large amounts of IL-1beta upon stimulation through TLR receptors in the absence of exogenous ATP

increased interleukin-17 secretion ( J:150053 )

• the large increase in Th17 cells leads to increased IL-17 secretion

increased interleukin-18 secretion ( J:150053 )

• macrophages and dendritic cells secrete large amounts of IL-18 upon stimulation through TLR receptors in the absence of exogenous ATP

increased anti-double stranded DNA antibody level ( J:150053 )

• anti-dsDNA antibodies are elevated in mice regardless if they are suffering from dermatitis or not

chronic inflammation ( J:150053 )

• as mice get older the develop chronic inflammation characterized by dermatitis and leukocyte infiltration of numerous tissues

dermatitis ( J:150053 )

• 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

enlarged liver ( J:150053 )

• mice suffering from dermatitis have enlarged livers with leukocyte infiltration

hematopoietic system

enlarged spleen ( J:150053 )

• mice suffering from dermatitis have enlarged spleens that contain increased numbers of neutrophils

abnormal CD4-positive, alpha-beta T cell number ( J:150053 )

• 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

increased T-helper 1 cell number ( J:150053 )

• the percentage of IFN-gamma producing T cells found in inflamed animals is increased compared to controls

increased leukocyte cell number ( J:150053 )

• white blood cell count is elevated in mice with dermatitis

increased activated T cell number ( J:150053 )

• CD4⁺ T cells isolated from mice suffering dermatitis have an activated phenotype (CD25^hi CD69^hi CD44^hi and CD62L^lo)

abnormal spleen red pulp morphology ( J:150053 )

• red pulp areas are filled with neutrophils and islands of trilineage hematopoietic cells

abnormal macrophage physiology ( J:150053 )

• 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

abnormal bone marrow cell physiology ( J:150053 )

• 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

dermatitis ( J:150053 )

• 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

Genotype
MGI:3850058

cn9

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Pycard^tm1Flv/Pycard^tm1Flv; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129 * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:150054 )

• mice appear phenotypically normal and do not develop the inflammatory disease that conditional heterozygotes develop on an intact Pycard background

Genotype
MGI:3850053

cn10

• Allelic Composition: Il1r1^tm1Roml/Il1r1^tm1Roml; Nlrp3^tm1Hhf/Nlrp3⁺; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

mortality/aging ( J:150054 )

N • postnatal lethality does not occur to mice on a IL-1 receptor null background

immune system

skin inflammation ( J:150054 )

• variable skin inflammation is observed

integument

skin inflammation ( J:150054 )

• variable skin inflammation is observed

Genotype
MGI:3850048

cn11

• Allelic Composition: Nlrp3^tm2Hhf/Nlrp3⁺; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:150054 )

• mice are either stillborn or day within one day of birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial cold autoinflammatory syndrome 1		DOID:0090062	OMIM:120100	J:150054

Genotype
MGI:3850056

cn12

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Rag1^tm1Mom/Rag1^tm1Mom; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:150054 )

• 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

slow postnatal weight gain ( J:150054 )

• mutant pups gained weight slowly, and then lost weight before dying

immune system

absent B cells ( J:150054 )

absent T cells ( J:150054 )

hematopoietic system

absent B cells ( J:150054 )

absent T cells ( J:150054 )

integument

reddish skin ( J:150054 )

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

scaly skin ( J:150054 )

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

Genotype
MGI:3850045

cn13

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:150054 )

• 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

slow postnatal weight gain ( J:150054 )

• mutant pups gained weight slowly, and then lost weight before dying

digestive/alimentary system

abnormal intestine morphology ( J:150054 )

• substantial necrosis occurs in the gut that is not associated with inflammation

renal/urinary system

abnormal kidney morphology ( J:150054 )

• substantial necrosis occurs in the kidney that is not associated with inflammation

immune system

increased leukocyte cell number ( J:150054 )

• white blood cell count is mildly elevated

increased neutrophil cell number ( J:150054 )

• pronounced neutrophilia is evident in these mice

abnormal circulating cytokine level ( J:150054 )

• GCSF is elevated in the sera of 6-8 day old mice

abnormal circulating chemokine level ( J:150054 )

• CXCL1 levels are elevated in the sera of mice 6-8 days old

increased circulating interleukin-1 beta level ( J:150054 )

• 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

increased circulating interleukin-18 level ( J:150054 )

• IL-18 levels are elevated in the sera of 6-8 day old mice

increased circulating interleukin-6 level ( J:150054 )

• 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

increased circulating tumor necrosis factor level ( J:150054 )

• TNF levels in the sera of 6-8 day old mice are elevated

increased inflammatory response ( J:150054 )

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

homeostasis/metabolism

abnormal circulating cytokine level ( J:150054 )

• GCSF is elevated in the sera of 6-8 day old mice

abnormal circulating chemokine level ( J:150054 )

• CXCL1 levels are elevated in the sera of mice 6-8 days old

increased circulating interleukin-1 beta level ( J:150054 )

• 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

increased circulating interleukin-18 level ( J:150054 )

• IL-18 levels are elevated in the sera of 6-8 day old mice

increased circulating interleukin-6 level ( J:150054 )

• 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

increased circulating tumor necrosis factor level ( J:150054 )

• TNF levels in the sera of 6-8 day old mice are elevated

hematopoietic system

thrombocytosis ( J:150054 )

• thrombocytosis is evident in these mice

increased leukocyte cell number ( J:150054 )

• white blood cell count is mildly elevated

increased neutrophil cell number ( J:150054 )

• pronounced neutrophilia is evident in these mice

integument

hairless ( J:150054 )

• hair growth does not occur in these mice

reddish skin ( J:150054 )

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

scaly skin ( J:150054 )

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

Genotype
MGI:3850052

cn14

• Allelic Composition: Nlrp3^tm2Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

immune system

abnormal macrophage physiology ( J:150054 )

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

abnormal dendritic cell physiology ( J:150054 )

• bone marrow derived dendritic cells (DCs) spontaneously secrete high levels of IL1-beta in response to cold (32 degrees) incubation

• DCs also hypersecrete the mature form of IL-1beta in response to activation

• the maximal response is 150-fold greater than controls

• DCs are able to secrete IL1-beta without the presence of exogenous ATP

hematopoietic system

abnormal macrophage physiology ( J:150054 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial cold autoinflammatory syndrome 1		DOID:0090062	OMIM:120100	J:150054

Genotype
MGI:3850050

cn15

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

immune system

abnormal macrophage physiology ( J:150054 )

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

abnormal dendritic cell physiology ( J:150054 )

• 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

abnormal dendritic cell antigen presentation ( J:150054 )

• 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

abnormal macrophage physiology ( J:150054 )

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

Genotype
MGI:3850044

cn16

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Tg(Zp3-cre)3Mrt/?
• Genetic Background: involves: 129/Sv * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:150054 )

• mice die between 2 and 14 days after birth probably due to multisystem organ failure secondary to inflammation and necrosis

growth/size/body

slow postnatal weight gain ( J:150054 )

• mutant pups gained weight slowly, and then lost weight before dying

immune system

increased leukocyte cell number ( J:150054 )

• white blood cell count is mildly elevated

increased neutrophil cell number ( J:150054 )

• pronounced neutrophilia is evident in these mice

increased inflammatory response ( J:150054 )

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

digestive/alimentary system

abnormal intestine morphology ( J:150054 )

• substantial necrosis occurs in the gut that is not associated with inflammation

renal/urinary system

abnormal kidney morphology ( J:150054 )

• substantial necrosis occurs in the kidney that is not associated with inflammation

hematopoietic system

thrombocytosis ( J:150054 )

• thrombocytosis is evident in these mice

increased leukocyte cell number ( J:150054 )

• white blood cell count is mildly elevated

increased neutrophil cell number ( J:150054 )

• pronounced neutrophilia is evident in these mice

integument

hairless ( J:150054 )

• hair growth does not occur in these mice

reddish skin ( J:150054 )

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

scaly skin ( J:150054 )

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

Genotype
MGI:3850051

cx17

• Allelic Composition: Nlrp3^tm2Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

growth/size/body

slow postnatal weight gain ( J:150054 )

• some older mice have slower weight gain

immune system

skin inflammation ( J:150054 )

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

integument

skin inflammation ( J:150054 )

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

Genotype
MGI:3850049

cx18

• Allelic Composition: Nlrp3^tm1Hhf/Nlrp3⁺; Tg(CAG-cre/Esr1*)5Amc/?
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA

growth/size/body

slow postnatal weight gain ( J:150054 )

• some older mice have slower weight gain

immune system

skin inflammation ( J:150054 )

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

integument

skin inflammation ( J:150054 )

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