Phenotypes Associated with This Genotype

Genotype
MGI:5517789

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

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

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