A murine model of HUS: Shiga toxin with lipopolysaccharide mimics the renal damage and physiologic response of human disease.
Hemolytic uremic syndrome (HUS), which is caused by Shiga toxin-producing Escherichia coli infection, is the leading cause of acute renal failure in children. At present, there is no complete small animal model of this disease. This study investigated a mouse model using intraperitoneal co-injection of purified Shiga toxin 2 (Stx2) plus LPS. Through microarray, biochemical, and histologic analysis, it was found to be a valid model of the human disease. Biochemical and microarray analysis of mouse kidneys revealed the Stx2 plus LPS challenge to be distinct from the effects of either agent alone. Microarrays identified differentially expressed genes that were demonstrated previously to play a role in this disease. Blood and serum analysis of these mice showed neutrophilia, thrombocytopenia, red cell hemolysis, and increased serum creatinine and blood urea nitrogen. In addition, histologic analysis and electron microscopy of mouse kidneys demonstrated glomerular fibrin deposition, red cell congestion, microthrombi formation, and glomerular ultrastructural changes. It was established that this C57BL/6 mouse is a complete model of HUS that includes the thrombocytopenia, hemolytic anemia, and renal failure that define the human disease. In addition, a time course of HUS disease progression that will be useful for identification of therapeutic targets and development of new treatments for HUS is described.
Keepers
Tiffany R
TR
University of Virginia, Department of Internal Medicine, Division of Nephrology, Box 800133, Charlottesville, VA 22908, USA.
Psotka
Mitchell A
MA
Gross
Lisa K
LK
Obrig
Tom G
TG
D000743:Anemia, Hemolytic / Q000209:etiology; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D022641:Shiga Toxin 2 / Q000633:toxicity*; D013921:Thrombocytopenia / Q000209:etiology; D015431:Weight Loss
D008070:Lipopolysaccharides; D022641:Shiga Toxin 2; D003404:Creatinine