Phenotype Image Detail

Image

Caption

Podocyte-specific deletion of Tjp1 results in glomerulosclerosis. (A) Kidney sections from Tjp1^tm1.1Whun/Tjp1^tm1.1Whun (Tjp1^flox/flox) and Tjp1^tm1.1Whun/Tjp1^tm1.1WhunTg(Nphs1-cre)33Mska/0 (Nphs1-Cre:Tjp1^flox/flox) mice were examined with the antibody against Tjp1. Tjp1 was specifically eliminated from podocytes, while it was detected in endothelial cells in the glomerulus in the conditional mutant mice (arrow). The expression of Tjp1 in the Bowman's capsule epithelial cells (double arrows) and in the renal tubules (arrowheads) was also unaffected. Scale bars, 10 um. (B-I) Analyses of the control (Tjp1^flox/flox) and conditional mutant mice at 6 weeks of age. The mutant mice exhibited significant growth retardation (B) and developed massive proteinuria (C). (D) Gross appearance of the kidneys from the control and mutant mice at 6 weeks of age. (E) Histological analyses with periodic acid-Schiff (PAS) staining displayed disorder in the tissue architecture of the mutant mice kidney (top panels). Severe glomerulosclerosis and proteinaceous casts in the dilated renal tubules were observed in the mutant mice, but not in control mice (bottom panels). Scale bars, 200 um (top panels), 20 um (bottom panels). (F) The number of sclerosed glomeruli was expressed as a percentage of the total number of glomeruli (mean +/- SEM of n = 3, **p<0.001). (G) Transmission electron micrographs showing the loss of slit diaphragms, destruction of foot processes, and aberrant glomerular basement membranes in the mutant mice. Scale bars, 2 um (top panels), 0.5 um (bottom panels). (H and I) Histopathological analyses by Jones' silver (H) and Masson's trichrome (I) stain. Global sclerosis with extensive deposits of basement membrane components were observed with both stains. Scale bars, 10 um.

Copyright

This image is from Itoh M, PLoS One 2014;9(9):e106621, and is displayed under the terms of the Creative Commons Attribution 4.0 International License. J:226210

Associated Alleles

Symbol	Name
Tg(Nphs1-cre)33Mska	transgene insertion 33, Taiji Matsusaka
Tjp1^tm1.1Whun	tight junction protein 1; targeted mutation 1.1, Walter Hunziker

Associated Genotypes

Allelic Composition	Genetic Background
Tjp1^tm1.1Whun/Tjp1^tm1.1Whun Tg(Nphs1-cre)33Mska/0	involves: C57BL/6 * C57BL/6N * DBA/2