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Distribution of meprin in kidneys from mice with high- and low-meprin activity
S S Craig1, J F Reckelhoff, J S Bond
1Department of Anatomy, Virginia Commonwealth University, Richmond 23298-0001.
Abstract:
An inherited deficiency of a metalloendopeptidase (meprin) activity occurs in kidneys of many inbred mouse strains. To clarify whether meprin protein is present in low-activity strains and determine the distribution of meprin in kidneys of mice with high- and low-meprin activities, kidney slices were stained through the use of the indirect immunoperoxidase technique and examined by light and electron microscopy. Light microscopy at high dilutions of anti-meprin IgG confirmed the brush border localization of meprin in high-meprin activity strains and revealed no detectable cross-reactive material in low-meprin activity strains. However, light and electron microscopy studies that use lower dilutions of anti-meprin immunoglobulin G (IgG) revealed cross-reactivity in low-activity strains, also at the luminal surface of the proximal tubules. Studies at lower magnifications indicated that meprin is primarily associated with the juxtamedullary region of the kidney in both high- and low-activity strains. Western blots of urinary proteins showed significant amounts of meprin-like proteins, but only in the urine of mice with high-meprin activity. The low activity of meprin in some inbred mouse strains is not associated with the presence of the protein in compartments of kidney cells other than the brush border or with secretion of the protein into the urine.
Insights
Meprin protein is present in the kidney brush border of low-activity mouse strains, despite reduced enzyme function. This localization, primarily in the juxtamedullary region, explains the inherited deficiency in meprin activity.
Area of Science:
- Nephrology
- Biochemistry
- Immunohistochemistry
Background:
- Inherited deficiencies in metalloendopeptidase (meprin) activity are observed in the kidneys of numerous inbred mouse strains.
- The precise localization and presence of meprin protein in low-activity strains remain unclear.
Purpose of the Study:
- To investigate the presence and distribution of meprin protein in mouse kidneys with varying meprin activity levels.
- To determine if low meprin activity correlates with altered protein localization or secretion.
Main Methods:
- Kidney slices from high- and low-meprin activity mouse strains were analyzed using indirect immunoperoxidase staining.
- Light and electron microscopy were employed to examine meprin localization within kidney tissues.
- Western blots were performed on urinary proteins to detect meprin-like proteins.
Main Results:
- Meprin protein was detected at the brush border of proximal tubules in low-activity strains, albeit with lower apparent levels than in high-activity strains.
- Meprin was primarily localized to the juxtamedullary region of the kidney in both high- and low-activity strains.
- Meprin-like proteins were found in the urine of high-activity mice but not in low-activity mice.
Conclusions:
- The reduced meprin activity in certain mouse strains is not due to the absence of the protein or its presence in abnormal cellular compartments.
- Meprin protein is present in the kidney brush border and juxtamedullary region even in strains with low enzymatic activity.
- Lack of urinary meprin excretion contributes to the observed low activity in affected mouse strains.