Research Description

Creation of a “Humanized” Mouse Model for IgA Nephropathy Immunoglobulin A

Nephropathy (IgAN) is characterized by mesangial deposition of Immunoglobulin A (IgA). The development of specific and targeted therapeutic agents for IgAN has been hampered by the absence of a suitable small animal model that has the ability to mimic human IgAN. For ease of study and genetic manipulation, a mouse model would be ideal. Preliminary studies have identified a clinical subtype of IgAN that develops in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, potentially due to a specific S. aureus surface antigen. I will create and purify recombinant staphylococcal aureus (MRSA) cell membrane antigen-GST fusion protein, which may induce IgA Nephropathy, immunize mice with the recombinant protein, draw blood samples, and harvest serum containing antibodies. These antibodies will be used to immunostain for the presence of MRSA antigens in the IgA-containing immune complex deposits in the mesangium. Additionally, urine will be tested for hematuria and proteinuria, while the kidneys will be examined by pathology and immunohistochemical staining will be done to detect for evidence of IgA deposition. The aims of my current study are to confirm the role of a specific S. aureus surface antigen in causing IgAN and to identify a mouse strain that lends itself to genetic manipulation and that can be induced to develop IgAN following immunization with a specific S. aureus surface antigen. The long-term goal is the creation of an inducible transgenic mouse model of human IgAN that expresses the human IgA1 subtype upon MRSA antigen immunization, representing the first “humanized” animal model of IgAN engineered to facilitate research and development of molecular diagnostics, prognostics and targeted therapy of this important disease.