FIGURE

Fig. 7

ID

ZDB-FIG-160823-1

Publication

Kuusela et al., 2016 - Tankyrase inhibition aggravates kidney injury in the absence of CD2AP

Other Figures

Fig. 7

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Fig. 7

Simultaneous disruption of cd2ap expression and tankyrase activity aggravates kidney injury in zebrafish larvae. (a and b) Knockdown of cd2ap with morpholino antisense oligonucleotides (cd2ap-MO) in zebrafish causes pericardial edema (arrowhead) at 5 days post fertilization (dpf) indicative of kidney dysfunction (b). Control-MO (C-MO)-injected larvae appear developmentally normal (a). (c and d) Inhibition of tankyrase activity with XAV939 in the cd2ap morphant between 3 and 5 dpf induces yolk sac edema and more severe pericardial edema (d, arrowhead) than knockdown of cd2ap alone (b), whereas XAV939 treatment has no effect on the control morphant (c). (e and g) Histological sections of 5 dpf control morphant (e) and control morphant treated with XAV939 (g) show normal glomeruli (arrowheads) and proximal convoluted tubules (arrows). (f) cd2ap morphant shows a disturbed glomerular structure (arrowhead) with cysts (asterisk). (h) Inhibition of tankyrase activity with XAV939 in cd2ap morphants leads to even more destructed glomerular structure with a dilated (asterisk) and stretched septal glomerulus in the midline (arrowhead) and dilated proximal convoluted tubule (arrow). (i) Immunoblotting for podocin and active β-catenin (ABC) in control morphants (C-MO) and cd2ap morphants (cd2ap-MO) with and without XAV939 treatment. α-Tubulin is included as a control. (j) Quantification of three replicate blots as in (i) shows significant downregulation of podocin and upregulation of ABC in cd2ap morphants compared with control morphants. XAV939 treatment further downregulates podocin in cd2ap morphants. (k) Knockdown of cd2ap with cd2ap-MO in zebrafish leads to an increase in total PARylation at 5 dpf compared with control-MO treated zebrafish. P-values were calculated with one-way ANOVA (**P<0.01; ***P<0.001). Scale bar: (e-h) 25 µm

Expression Data

Genes:	ctnnb1 nphs2
Antibodies:	Ab2-nphs2 Ab3-ctnnb1
Fish:	WT WT + MO1-cd2ap
Condition:	chemical treatment: XAV939
Knockdown Reagent:	MO1-cd2ap
Anatomical Term:	whole organism
Stage:	Day 5

Expression Detail

Antibody Labeling

Phenotype Data

Fish:	WT + MO1-cd2ap
Condition:	chemical treatment: XAV939
Knockdown Reagent:	MO1-cd2ap
Observed In:	pericardium pronephric capsular space pronephric glomerular capillary pronephric glomerulus protein poly-ADP-ribosylation proximal convoluted tubule whole organism yolk syncytial layer
Stage:	Day 5

Phenotype Detail

Acknowledgments

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