Certain mouse strains are deficient in a kidney brush-border metallo-endopeptidase activity

Area of Science:

• Biochemistry
• Renal Physiology
• Enzymology

Background:

• Microvilli preparations from BALB/c mouse kidneys contain an alkaline metallo-endopeptidase known as meprin.
• Several genealogically related inbred mouse strains exhibit a marked deficiency in meprin activity.
• Meprin deficiency is specific, as other brush-border enzymes like alkaline phosphatase and aminopeptidase M remain at normal levels in deficient strains.

Purpose of the Study:

• To investigate the nature of meprin deficiency in specific inbred mouse strains.
• To determine if the deficiency affects other renal brush-border enzymes.
• To explore potential causes for meprin deficiency, such as pH optimum shifts or inhibitors.

Main Methods:

• Enzyme activity assays on microvilli preparations from different mouse strains.
• Comparison of meprin activity levels between normal and deficient strains.
• Assessment of other brush-border enzyme activities (alkaline phosphatase, aminopeptidase M, neutral endopeptidase) in deficient strains.

Main Results:

• Meprin-deficient strains (CBA/J and C3H/HeJ) were identified.
• These strains showed normal activity of other brush-border enzymes, including alkaline phosphatase, aminopeptidase M, and a phosphoramidon-sensitive neutral endopeptidase.
• The deficiency was not explained by a shift in the enzyme's pH optimum or the presence of endogenous inhibitors.

Conclusions:

• Meprin deficiency in certain inbred mice is a specific enzymatic defect.
• The deficiency is not due to a lack of other brush-border enzymes or the presence of inhibitors.
• The findings suggest a genetic basis for meprin deficiency in these mouse models, impacting renal metallo-endopeptidase activity.