Cryopyrin Associated Periodic Syndromes (CAPS) are a spectrum of autoinflammatory diseases associated with fever, neutrophilic rash, arthralgia, and leukocytosis. The most severe patients also develop CNS inflammation leading to hearing loss and seizures and/or bone pathology including infantile-onset cartilage overgrowth of the distal femur and generalized osteopenia. Most patients with CAPS have gain-of-function mutations in NLRP3 resulting in dysregulation of the inflammasome and systemic inflammation due to increased release of cytokines such as IL-1B. This pathophysiology is supported by the excellent clinical response of CAPS patients to IL-1B targeted therapy, however the bone disease is less treatment responsive.  Further investigations to dissect these pathways were performed in conditional knockin mice developed with CAPS patient mutations which also develop neutrophilic inflammation in the same tissues and a unique bone phenotype. These knockin mice have been bred with various Cre mice to determine the pathogenic cells involved and also bred onto mice deficient in several key downstream genes.