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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2016 ; 311
(5
): F1015-F1024
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Characterization and phosphoproteomic analysis of a human immortalized podocyte
model of Fabry disease generated using CRISPR/Cas9 technology
#MMPMID27681560
Pereira EM
; Labilloy A
; Eshbach ML
; Roy A
; Subramanya AR
; Monte S
; Labilloy G
; Weisz OA
Am J Physiol Renal Physiol
2016[Nov]; 311
(5
): F1015-F1024
PMID27681560
show ga
Fabry nephropathy is a major cause of morbidity and premature death in patients
with Fabry disease (FD), a rare X-linked lysosomal storage disorder. Gb3, the
main substrate of ?-galactosidase A (?-Gal A), progressively accumulates within
cells in a variety of tissues. Establishment of cell models has been useful as a
tool for testing hypotheses of disease pathogenesis. We applied CRISPR/Cas9
genome editing technology to the GLA gene to develop human kidney cell models of
FD in human immortalized podocytes, which are the main affected renal cell type.
Our podocytes lack detectable ?-Gal A activity and have increased levels of Gb3.
To explore different pathways that could have distinct patterns of activation
under conditions of ?-gal A deficiency, we used a high-throughput antibody array
to perform phosphorylation profiling of CRISPR/Cas9-edited and control podocytes.
Changes in both total protein levels and in phosphorylation status per site were
observed. Analysis of our candidate proteins suggests that multiple signaling
pathways are impaired in FD.
|*Clustered Regularly Interspaced Short Palindromic Repeats
[MESH]