ALTERED MESSENGER-RNA EXPRESSION OF BASEMENT-MEMBRANE COMPONENTS IN A MURINE MODEL OF POLYCYSTIC KIDNEY-DISEASE

  • 1 March 1988
    • journal article
    • research article
    • Vol. 58  (3) , 262-269
Abstract
Basement membranes surround the renal tubules and have been shown to limit their distension in vitro. Therefore, it has been postulated that a defect in a basement membrane component(s) underlies the pathogenesis of polycystic kidney disease. Here we have studied a murine model of congenital polycystic kidney disease and found by immunohistology, that the components of the peri-cyst basement membrane appeared to diminish with time. We also measured mRNA levels for collagen IV and laminin, and found a different pattern than in the normal mouse kidney. In normal kidneys, mRNA levels for the B1 and B2 chains of laminin were maximal at birth, and at 1 week for the .alpha.1(IV) chain of collagen IV. With all three chains, the levels then rapidly declined. In contrast, mRNA for the .alpha.1(IV) chain in congenital polycystic kidneys was half normal 1 week after birth and then increased. Laminin B1 and B2 chain mRNA''s were 80% of normal at 1 week but were maintained at that level. As a control, .beta.-actin mRNA was examined and found to remain constant in both normal and diseased kidneys. In situ hybridization of cRNA probes for the .alpha.1(IV) chain confirmed that cells associated with cysts were the principal source of expression of these basement membrane mRNAs. Thus, there exists an abnormal regulation of basement membrane gene expression in congenital polycystic kidney disease. The first stage is characterized by reduced levels of expression. In the second stage, the levels are abnormally high, perhaps representing a compensatory synthesis of basement membrane as cysts enlarge.