| First Author | Li D | Year | 2021 |
| Journal | Hum Mol Genet | Volume | 31 |
| Issue | 2 | Pages | 232-243 |
| PubMed ID | 34415307 | Mgi Jnum | J:324503 |
| Mgi Id | MGI:7277788 | Doi | 10.1093/hmg/ddab239 |
| Citation | Li D, et al. (2021) An Nphp1 knockout mouse model targeting exon 2-20 demonstrates characteristic phenotypes of human nephronophthisis. Hum Mol Genet 31(2):232-243 |
| abstractText | Nephronophthisis (NPH) is the most prevalent monogenetic disorder leading to end-stage renal failure (ESRD) in childhood. Mutations in Nphp1, encoding a cilia-localized protein, account for the majority of NPH cases. Despite its identification many years ago, Nphp1 deletions targeting exon 4 or exon 20 have not reproduced the histological features of human NPH in murine models. In this study, we deleted exon 2-20 of Nphp1 by CRISPR/Cas9 gene editing to create a near-total knockout (KO) mouse model (Nphp1del2-20/del2-20). Nphp1del2-20/del2-20 mice faithfully reproduced the renal and extrarenal phenotypes associated with human NPH, including renal cyst development, tubular basement membrane thickening, retinal degeneration and abnormal spermatogenesis. Importantly, Nphp1 re-expression using an adenoviral-associated-virus-9 vector could partially rescue both renal and retinal phenotypes in Nphp1del2-20/del2-20 mice. Our results reported the first relevant Nphp1 mouse model with renal phenotypes for human disease. It will be a valuable model for future studies of Nphp1 function and to develop novel treatments for this common childhood disease. |
