Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate
Bryan L. Wharram, Meera Goyal, Patrick J. Gillespie, Jocelyn E. Wiggins, David B. Kershaw, Lawrence B. Holzman, Robert C. Dysko, Thomas L. Saunders, Linda C. Samuelson, Roger C. Wiggins
Bryan L. Wharram, Meera Goyal, Patrick J. Gillespie, Jocelyn E. Wiggins, David B. Kershaw, Lawrence B. Holzman, Robert C. Dysko, Thomas L. Saunders, Linda C. Samuelson, Roger C. Wiggins
View: Text | PDF
Article

Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate

Abstract

Glomerular epithelial protein 1 (GLEPP1) is a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte. The GLEPP1 gene (Ptpro) was disrupted at an exon coding for the NH2-terminal region by gene targeting in embryonic stem cells. Heterozygote mating produced the expected genotypic ratio of 1:2:1, indicating that the Ptpro–/– genotype does not lead to embryonic or neonatal lethality. Kidney and glomerular structure was normal at the gross and light microscopic levels. Scanning and transmission electron microscopy showed that Ptpro–/– mice had an amoeboid rather than the typical octopoid structure seen in the wild-type mouse podocyte and that there were blunting and widening of the minor (foot) processes in association with altered distribution of the podocyte intermediate cytoskeletal protein vimentin. Reduced filtration surface area in association with these structural changes was confirmed by finding reduced glomerular nephrin content and reduced glomerular filtration rate in Ptpro–/– mice. There was no detectable increase in the urine albumin excretion of Ptpro–/– mice. After removal of one or more kidneys, Ptpro–/– mice had higher blood pressure than did their wild-type littermates. These data support the conclusion that the GLEPP1 (Ptpro) receptor plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function.

Authors

Bryan L. Wharram, Meera Goyal, Patrick J. Gillespie, Jocelyn E. Wiggins, David B. Kershaw, Lawrence B. Holzman, Robert C. Dysko, Thomas L. Saunders, Linda C. Samuelson, Roger C. Wiggins

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Scanning electron micrographs of glomeruli made at different magnificati...
Scanning electron micrographs of glomeruli made at different magnifications, with the wild-type (Ptpro+/+) mice shown in the left three panels and Ptpro–/– mice shown in the right three panels. The major processes seen in Ptpro–/– mice were broader, wider, and less distinct than the narrower, more well-defined major processes seen in the wild-type mice. The overall structure of the Ptpro–/– podocytes is more amoeba-like compared with the octopus-like structure of the wild-type (×3,000, top panels). At high power the foot processes of the Ptpro+/+ mice can be seen to be regular and fingerlike in appearance in contrast to the broader, shorter (more toelike) foot processes found in the Ptpro–/– mice (×10,000, bottom panels).