A PSTPIP1 knockout mouse for use in the study of autoinflammation or PAPA syndrome
The US National Institutes of Health estimate that nearly 23.5 million Americans suffer from autoimmune disease with the prevalence on the rise. The PSTPIP1 gene in mice encodes the proline-serine-threonine phosphatase-interacting protein 1, also known as CD2 binding protein 1 (CD2BP1). Mutations in the human homologue result in a hyper-responsive immune system and cause pyogenic arthritis with poderma gangrenosum and acne (PAPA) syndrome, due to its interaction with pyrin and a protein tyrosine phosphatase known to regulate both the innate and adaptive immune response, primarily in granulocytes. This technology is a knockout mouse model of PSTPIP1 for the study of PAPA syndrome or any disorder known to cause promiscuous activation of the immune response. Mice homozygous for the knock-out allele exhibit hyper-responsive T cells upon antigen receptor stimulation.
Study multiple candidate drugs or pathways that mediate an autoinflammatory response
The etiology and biochemical pathways of PSTPIP1 mutations overlap with many autoimmune disorders such as rheumatoid arthritis, familial Mediterranean fever, Hyperimmunoglobulinemia D with recurrent fever, Muckle-Wells syndrome, neonatal onset multisystem inflammatory disease, familial cold urticarial, and inflammatory bowel disease. Given that so many autoinflammatory disorders are associated with the PSTPIP1 pathway, the technology is ideally suited to study mammalian candidate drug response to immunosupressants targeted at a number of signaling molecules including tumor necrosis factor (TNF) and interleukin-1 (IL1).
The mouse model was engineered and tested in a laboratory.
Lead Inventor:
Applications:
- Mammalian model to investigate the basis of PAPA syndrome
- Model the function of the PSTPIP1 gene
- Screening of immunosuppressants or other drugs known to mediate immune function
- Investigate the response to pro- or anti-inflammatory drugs
Advantages:
- Mouse models are inexpensive ways to study a mammalian response
- A single mouse strain may be used to study multiple disease models, pathways, and candidate drug responses
Patent information:
Patent Pending
Tech Ventures Reference: IR CU14295