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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
An electron microscope study of kidney basement membrane changes in the mouse by lipoteichoic acid from Streptococcus
1Department of Microbiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Abstract:
Mice injected repeatedly, intraperitoneally or intravenously, for approximately 1 month with a total of 1.04 mg lipoteichoic acid from a nephritogenic strain of Streptococcus pyogenes lost weight. Analysis by electron microscopy revealed that they also exhibited extensive kidney changes in basement membrane morphology which resembled, in part, those observed in human poststreptococcal glomerulonephritis. For example, the glomerular basement membrane became electron dense and exhibited at least a twofold increase in width sporadically within the same preparation after exposure to lipoteichoic acid. Also, whereas appreciable loss or reduction in epithelial foot processes as a result of fusion was clearly evident, epithelial slits and slit membranes or diaphragms between normal foot processes were not selectively affected. In addition, another mostly thickened, highly coiled or serpentinelike basement membrane with amorphous nodules appeared in these preparations. This type membrane was not observed surrounding the capillary lumina and was the most pronounced abnormality apparent in almost all preparations from mice exposed to lipoteichoic acid. Likewise, the proximal tubular basement membrane became variable in width and increased in electron density in mice given lipoteichoic acid as compared with controls. In addition, this membrane was often punctuated with various morphological protrusions originating from only its thickened areas and which extended away from, and not into, the capillary space. This change was only associated with the basement membrane of the proximal tubular capillaries. All membrane changes persisted but gradually subsided, with normal kidney membrane morphology reappearing on the 4th day following the last injection of lipoteichoic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Mice exposed to lipoteichoic acid developed kidney abnormalities mimicking human poststreptococcal glomerulonephritis. These changes, including thickened basement membranes, resolved after injections ceased.
Area of Science:
- Nephrology
- Immunology
- Microbiology
Background:
- Poststreptococcal glomerulonephritis is a kidney disease following Streptococcus pyogenes infection.
- Lipoteichoic acid is a major component of Gram-positive bacterial cell walls.
Purpose of the Study:
- To investigate the effects of lipoteichoic acid from Streptococcus pyogenes on kidney morphology in mice.
- To determine if these effects resemble changes seen in human poststreptococcal glomerulonephritis.
Main Methods:
- Mice were injected with lipoteichoic acid from a nephritogenic Streptococcus pyogenes strain.
- Kidney tissues were analyzed using electron microscopy.
Main Results:
- Mice showed weight loss and significant kidney basement membrane changes.
- Glomerular basement membranes became electron-dense and widened; thickened, serpentinelike membranes with nodules also appeared.
- Proximal tubular basement membranes showed variable width, increased density, and protrusions.
Conclusions:
- Lipoteichoic acid exposure induces kidney damage in mice resembling human poststreptococcal glomerulonephritis.
- The observed basement membrane alterations are a key feature of this induced nephropathy.
- Kidney morphology normalized gradually after cessation of lipoteichoic acid injections.

