Pkd1-Flox/Cdh16-CreERT2

Fig.1 Detection of Pkd1 expression in the kidney by qPCR. Each value in G1, G2, G3, G4 and G5 represents the mRNA level relative to the value in G1 (n=4-7 males and females). Tamoxifen induction was initiated in all mice starting on postnatal day 25 (week 0). At 12 weeks after Tamoxifen induction, all mice were sacrificed, and the isolated kidneys were subjected to detect the Pkd1 expression in the kidney by qPCR.

Fig.2 The body weight of Pkd1^Flox/Flox; Cdh16-CreERT2 mice. Tamoxifen induction was initiated in all mice starting on postnatal day 25 (n=4-8 males and females).

Fig.3 Blood biochemical results of Pkd1^Flox/Flox; Cdh16-CreERT2 mice. Tamoxifen induction was initiated in all mice starting on postnatal day 25 (week 0). Starting at week 4, blood samples were collected and subjected to biochemical analysis at two-week intervals (n=4-8 males and females). At 12 weeks after Tamoxifen induction, male Pkd1^Flox/Flox; Cdh16-CreERT2 exhibited significantly elevated levels of UREA and CREA. *p<0.05, **p<0.01 in control group treatment with G1 versus G3, #p<0.05, ##p<0.01 in control group treatment with G1 versus G4.

Fig.4 Urinary biochemical results of Pkd1^Flox/Flox; Cdh16-CreERT2 ADPKD mice. Tamoxifen induction was initiated in all mice starting on postnatal day 25 (week 0). Starting at week 4 after Tamoxifen induction, urine samples were collected and subjected to biochemical analysis at two-week intervals (n=4-8 males and females). At 4 weeks after Tamoxifen induction, Pkd1^Flox/Flox; Cdh16-CreERT2 exhibited significantly elevated levels of mALB and UACR. **p<0.01, ***p<0.001 in control group treatment with G1 versus G3, ##p<0.01, ###p<0.001 in control group treatment with G1 versus G4, && p<0.01, &&&p<0.001 in control group treatment with G2 versus G5. 

Fig.5 Phenotype analysis of kidney in Pkd1^Flox/Flox; Cdh16-CreERT2 ADPKD mice. Tamoxifen induction was initiated in all mice starting on postnatal day 25 (week 0). At 12 weeks after Tamoxifen induction, all mice were sacrificed, and the isolated kidneys were subjected to weight and photograph (n=4-8 males and females). Notable increase in kidney volume and weight was observed in Pkd1^Flox/Flox; Cdh16-CreERT2 mice at 12 weeks post-induction. ***p<0.001 in control group treatment with G1 versus G3, ###p<0.001 in control group treatment with G1 versus G4, &&&p<0.001 in control group treatment with G2 versus G5. 

Fig.6 Pathological analysis of kidney in Pkd1^Flox/Flox; Cdh16-CreERT2 ADPKD mice. At 12 weeks after Tamoxifen induction, all mice were sacrificed, and the isolated kidneys were subjected to embed in paraffin with HE staining. The Pkd1^Flox/Flox; Cdh16-CreERT2 mice exhibited a pronounced renal pathology compared to controls, featuring numerous cysts, tubular protein casts, evident fibrosis, and significant interstitial inflammatory cell infiltration. Quantification of cyst area confirmed a significantly higher cyst index in Pkd1^Flox/Flox; Cdh16-CreERT2 mice. Notably, these pathological manifestations were significantly more accentuated in male mice. 

Note: cyst (Blue), protein casts (Red), fibrosis (Yellow), inflammatory cell infiltration (Black). First row: Scale Bar=2000 μm, Second row: Scale Bar=500 μm. (n=3-5 males and females). ***p<0.001 in control group treatment with G1 versus G3, &&&p<0.001 in control group treatment with G2 versus G5. 

Fig.7 Pathological analysis of Liver in Pkd1^Flox/Flox; Cdh16-CreERT2 ADPKD mice. At 12 weeks after Tamoxifen induction, all mice were sacrificed, and the isolated livers were subjected to embed in paraffin with HE staining. The results revealed significant pathological phenotypes in the liver of Pkd1^Flox/Flox; Cdh16-CreERT2 mice compared to control mice, including the presence of multiple hepatic cysts, biliary fibrosis, and interstitial inflammatory cell infiltration. Notably, these pathological manifestations were significantly more accentuated in male mice. 

Note: cyst (Blue), fibrosis (Yellow). Scale Bar=200 μm. (n=3-5 males and females). **p<0.01 in control group treatment with G1 versus G3, &p<0.05 in control group treatment with G2 versus G5. 

Fig.8 Pathological analysis of pancreas in Pkd1^Flox/Flox; Cdh16-CreERT2 ADPKD mice. At 12 weeks after Tamoxifen induction, all mice were sacrificed, and the isolated pancreas were subjected to embed in paraffin with HE staining. The results of pancreatic sections revealed significant architectural abnormalities compared to the control group, manifesting as occasional cystic change, pronounced stromal fibrosis, and extensive interstitial infiltration by inflammatory cells. Notably, these pathological manifestations were significantly more accentuated in male mice.

Note: cyst (Blue), fibrosis (Yellow), inflammatory cell infiltration (Black). Scale Bar=200 μm. (n=3-5 males and females). &p<0.05 in control group treatment with G2 versus G5.