Introduction:

• The Pkd1 gene encodes polycystin‑1 (PC1), a transmembrane receptor essential for renal tubular architecture, ciliary signaling and epithelial cell homeostasis. In B‑Pkd1 flox/fl; CAG‑iCreERT2 mice, tamoxifen‑driven Pkd1 deletion abolishes PC1 function, resulting in dysregulated cell proliferation, tubular dilation, intratubular casts and progressive cyst formation in kidney and liver.

Gene targeting strategy:

• B-Pkd1 flox, CAG-iCreERT2 mice were obtained by mating B-Pkd1 flox mice (114146) and B-CAG-iCreERT2 mice (110147).
• Upon tamoxifen induction, Pkd1 is globally deleted in all tissues.

mRNA expression analysis:

• At 10 weeks post-tamoxifen administration, the mRNA expression of Pkd1 was significantly reduced.

Serum biochemistry analysis:

• Compared with the control group, tamoxifen‑induced mice exhibited markedly increased serum urea and creatinine levels at 16 weeks post‑induction, while no obvious differences were observed at earlier time‑points.

Urine biochemistry analysis:

• Compared with the control group, tamoxifen‑induced mice showed significantly elevated urinary mALB and UACR.

H&E analysis:

• Tamoxifen‑induced deletion of Pkd1 in B‑Pkd1 flox, CAG‑iCreERT2 mice triggered prominent hepatic and renal cystic pathology as early as 10 weeks post‑induction, with cyst burden, tubular dilation, intratubular casts and interstitial injury further exacerbated at 16 weeks post‑induction.

Application:

• B‑Pkd1 flox, CAG‑iCreERT2 mice are a well-established mouse model for ADPKD. This product is used for pharmacodynamics and safety evaluation of kidney diseases such as ADPKD.

Gene targeting strategy for B-Pkd1 flox, CAG-iCreERT2 mice.

B-Pkd1 flox, CAG-iCreERT2 mice were obtained by mating B-Pkd1 flox mice (114146) and B-CAG-iCreERT2 mice (110147).

Upon tamoxifen induction, Pkd1 is globally deleted in all tissues.

Strain specific analysis of Pkd1 gene expression in B-Pkd1 flox, CAG-iCreERT2 mice by RT-qPCR. Kidney RNA was isolated from homozygous B-Pkd1 flox, CAG-iCreERT2 mice (flox/flox, KI/+) (male, 7w, n=3). At 10 weeks post-tamoxifen administration (100 mpk), the mRNA expression of Pkd1 was significantly reduced. Values are expressed as mean ± SEM. Analyzed by 2 way-ANOVA, *P<0.05, **P<0.01, ***P<0.001.

Serum biochemistry analysis of B-Pkd1 flox, CAG-iCreERT2 mice. Serum UREA and creatinine (CREA) levels were longitudinally monitored in B-Pkd1 flox, CAG-iCreERT2 mice (flox/flox, KI/+). G1 served as corn oil‑treated vehicle control and G2 received tamoxifen (TAM, 100 mg/kg). Serum samples were collected at 5, 7, 10, 13 and 16 weeks post-induction. Compared with the control group, tamoxifen‑induced mice exhibited markedly increased serum urea and creatinine levels at 16 weeks post-induction, while no obvious differences were observed at earlier time‑points. Values are expressed as mean ± SEM.

Urine biochemistry analysis of B-Pkd1 flox, CAG-iCreERT2 mice. Urinary mALB and UACR levels were detected in B‑Pkd1 flox, CAG‑iCreERT2 mice (flox/flox, KI/+). G1 served as corn‑oil‑treated vehicle control and G2 received tamoxifen (TAM, 100 mg/kg). Compared with the control group, tamoxifen‑induced mice showed significantly elevated urinary mALB and UACR at 16 weeks post-induction. Values are expressed as mean ± SEM. Analyzed by 2‑way‑ANOVA, *P<0.05, **P<0.01, ***P<0.001.

H&E analysis in wild-type C57BL/6JNifdc and B-Pkd1 flox, CAG-iCreERT2 mice. At 10 weeks post-tamoxifen administration, animals were sacrificed, and their livers and kidneys were processed for histopathological analysis. Induced mice developed pronounced pathological lesions in liver and kidney relative to controls: the liver displayed widespread cysts and prominent biliary hyperplasia, whereas the kidney showed focal cyst formation, dilated renal tubules, and intratubular casts. Red arrows: Tubular casts; Blue arrows: Cysts.

H&E analysis in wild-type C57BL/6JNifdc and B-Pkd1 flox, CAG-iCreERT2 mice. At 16 weeks post tamoxifen administration, animals were sacrificed, and their livers and kidneys were processed for HE histopathological analysis. Compared with corn‑oil‑treated control group (G1), tamoxifen‑induced mice (G2) exhibited more severe pathological lesions in both liver and kidney: the liver showed extensive cystic lesions; the kidney displayed widespread cyst formation, massive renal tubular dilation and intratubular casts. Red arrows: Tubular casts; Blue arrows: Cysts.