title: Lupus-like kidney disease in mice deficient in the Src family tyrosine kinases Lyn and Fyn.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease whose cause is poorly understood. Mice rendered deficient in specific genes have served as useful animal models in deciphering the genetic control of the disease [1]. We [2] and others [3, 4] previously demonstrated that mice deficient in the Src family tyrosine kinase Lyn developed a mild lupus-like disease with high survival rates. During the course of investigating the functional interaction of Src family kinases, we generated a mouse strain deficient in both Lyn and Fyn. The double-mutant mice died at relatively young ages and developed a severe lupus-like kidney disease. Unlike the double-mutant mice, single mutants deficient in either Lyn or Fyn lived longer and had distinct subsets of the symptoms found in the former. Lyn deficiency led to high levels of autoantibody production and glomerulonephritis, as previously reported [2--4], whereas loss of Fyn contributed to proteinuria by a B and T lymphocyte-independent mechanism. Our data suggest that the severe kidney disease in the double-mutant mice results from a combination of immunological and kidney-intrinsic defects. This new animal model may be informative about the causes of human SLE.
authors.affiliation: G. W. Hooper Foundation, University of California, San Francisco, CA 94143, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Yu
authors.forename: T S
authors.initials: TS
authors.lastname: Yen
authors.forename: C A
authors.initials: CA
authors.lastname: Lowell
authors.forename: A L
authors.initials: AL
authors.lastname: DeFranco
mesh_terms: D000818:Animals; D008181:Lupus Nephritis / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases