A MOUSE MODEL FOR AUTOIMMUNE LUPUS GLOMERULONEPHRITIS

Systemic Lupus Erythematosus is an autoimmune disease which affects many organs and has a wide range of clinical manifestations. The disease is characterized by joint pain, rashes, and fevers, as well as inflammation of organs including the heart, lungs and kidneys. The cause of lupus has been difficult to identify, as almost every pathway of the immune system is abnormal in effected individuals. The production of auto-antibodies is thought to be largely responsible for the observed pathology; however, there is recent evidence that T lymphocytes promote and mediate the progression of the disease.

Severe glomerulonephritis (inflammation of the tiny filters of the kidney) is a serious complication of lupus which can lead to kidney dysfunction. Researchers at UCSF have developed a strain of mice which develop phenotypes characteristic of autoimmune glomerulonephritis. This strain was created by genetically modifying a key T-cell signalling molecule, resulting in a lack of negative regulation of the immune system. The mice develop autoimmune glomerulonephritis within 2-3 months of birth and display pathological features similar to those found in human lupus: progressive glomerular scarring, immunoglobulin deposition, subepithelial and subendothelial deposits and anti-dsDNA antibodies in the serum. The lack of negative T-cell regulation in these mice may make them useful as models for other immune disorders as well. When bred onto different genetic backgrounds or challenged with tissue specific antigens, these mice may be susceptible to other types of autoimmunity.

This mouse model system offers the following advantages:

• Develop autoimmune glomerulonephritis with symptoms similar to those observed in human lupus.
• Develop symptoms faster (within 2-3 months of birth) than current murine lupus models, such as NZB/NZW mice, and on a simpler genetic background
• May be useful as a model for other types of autoimmunity when bred onto different genetic backgrounds or stimulated with tissue-specific antigens.

Reference:

Majeti R, et al. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell, 2000; 103(7):1059-1070.

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Anson Nomura, Ph.D.
Licensing Officer
Tel: 415-353-4626
anson.nomura@ucsf.edu

Reference: OTM Case #SF2000-044