Introduction:

• The Pkd1 gene encodes polycystin‑1 (PC1), a transmembrane receptor critical for maintaining renal tubular structure, ciliary signaling, and normal epithelial cell proliferation and differentiation. Although designated R3277C in the mouse model to match the human variant nomenclature, this mutation affects the homologous residue at position 3269 in the mouse PC1 protein. This missense mutation disrupts the normal function of polycystin‑1, leading to dysregulated cell growth, abnormal tubular dilation, and progressive cyst formation in the kidneys, thereby faithfully recapitulating the core pathological features of human polycystic kidney disease.

Gene targeting strategy:

• The exon 2 of mouse Pkhd1 gene were knocked out in B-Pkhd1 KO mice.

mRNA expression analysis:

• Full length mouse Pkhd1 mRNA were detected in C57BL/6JNifdc, while Pkhd1 mRNA with exon 2 deletion was detected in homozygous B-Pkhd1 KO mice, confirmed via Sanger sequencing.

H&E analysis:

• The liver of B-Pkhd1 KO mice showed multiple cysts. No significant histopathological changes were observed in the kidneys.

Application:

• B-Pkhd1 KO mice is a well-established mouse model for autosomal recessive polycystic kidney disease (ARPKD). This product is used for pharmacodynamics and safety evaluation of kidney diseases such as ARPKD.

Gene targeting strategy for B-Pkhd1 KO mice. The exon 2 of mouse Pkhd1 gene were knocked out in B-Pkhd1 KO mice.

Strain specific analysis of Pkhd1 mRNA expression in wild-type C57BL/6JNifdc and B-Pkhd1 KO mice by RT-PCR. Tissue RNA were isolated from wild-type C57BL/6JNifdc (+/+) and homozygous B-Pkhd1 KO mice(-/-), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse Pkhd1 primers. Full length mouse Pkhd1 mRNA were detected in C57BL/6JNifdc, while Pkhd1 mRNA with exon 2 deletion was detected in homozygous B-Pkhd1 KO mice, confirmed via Sanger sequencing.

H&E analysis in wild-type C57BL/6JNifdc and B-Pkhd1 KO mice. The liver and kidney tissues of wild-type C57BL/6JNifdc mice (+/+) and homozygous B-Pkhd1 KO mice (-/-) were isolated at 33 weeks old and analyzed with H&E staining (male, n=3). The liver of B-Pkhd1 KO mice showed multiple cysts. No significant histopathological changes were observed in the kidneys. Blue arrows: cyst.