Kidney Week

Abstract: SA-PO0126

Phenotypic Characterization of Retinal Degeneration in an Nphp1 Knockout Mouse Model

Session Information

• ADPKD and Cystic Kidney Disease - 3
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Marchuk, Daniel, Boston Children's Hospital, Boston, Massachusetts, United States

Daniel Marchuk, MD

• Lomjansook, Kraisoon, Boston Children's Hospital, Boston, Massachusetts, United States

Kraisoon Lomjansook, MD

• Balbach, Maximilian, Boston Children's Hospital, Boston, Massachusetts, United States

Maximilian Balbach

• Szczepan, Manon, Boston Children's Hospital, Boston, Massachusetts, United States

Manon Szczepan, MSc, PhD

• Hirst, Victoria, Boston Children's Hospital, Boston, Massachusetts, United States

Victoria Hirst

• Komatsu, Hiroyuki, Boston Children's Hospital, Boston, Massachusetts, United States

Hiroyuki Komatsu, PhD, DVM

• Lee, Michelle, Boston Children's Hospital, Boston, Massachusetts, United States

Michelle Lee

• Zion, Elena, Boston Children's Hospital, Boston, Massachusetts, United States

Elena Zion, MD

• Riedhammer, Korbinian M., Boston Children's Hospital, Boston, Massachusetts, United States

Korbinian M. Riedhammer, MD

• Prakash, Chiranth M., Boston Children's Hospital, Boston, Massachusetts, United States

Chiranth M. Prakash, PhD

• Franken, Gijs A.C., Boston Children's Hospital, Boston, Massachusetts, United States

Gijs A.C. Franken

• Madariaga, Leire, Boston Children's Hospital, Boston, Massachusetts, United States

Leire Madariaga, MD

• Saida, Ken, Boston Children's Hospital, Boston, Massachusetts, United States

Ken Saida, MD, PhD

• Sun, Ye, Boston Children's Hospital, Boston, Massachusetts, United States

Ye Sun, MD, PhD

• Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Friedhelm Hildebrandt, MD

Background

Biallelic NPHP1 loss of function variants cause nephronophthisis (NPHP), a monogenic renal ciliopathy that causes chronic kidney disease (CKD) in adolescence. Around ~10% of cases are associated Senior-Løken syndrome (SLS) characterized by both NPHP and retinitis pigmentosa like retinal dystrophy, which leads to progressive vision loss.

Methods

We sought to quantify phenotypic parameters of retinal degeneration in Nphp1^-/- mice for future assessment of therapeutic efficacy in gene therapy studies. We studied a previously developed mouse model of Nphp1 loss, Nphp1^tm1Jgg/J (JAX:013169; Louie Nat Genet. 42:175, 2010). Optical coherence tomography (OCT), electroretinography (ERG), and retinal histopathologic analysis were used to determine the time course of retinal degeneration between 3 and 24 weeks of age.

Results

OCT analysis demonstrated progressive retinal thinning in the Nphp1^-/- knockout mice as early as 3 weeks of age (Fig. 1A). Histologic analysis showed thinning of the outer nuclear layer containing the photoreceptor cell bodies (Fig. 1B) consistent with photoreceptor degeneration observed in SLS. Functional assessment using dark-adapted ERG (Fig. 2) showed impaired retinal response in Nphp1^-/- knockout mice. A specific response component (amplitudes of the third response peak, RmP3) in the ERG waveform was significantly decreased at 3,4, and 6 weeks of age consistent with the rod dysfunction of SLS.

Conclusion

Using three different methods (OCT, histology, and ERG), we identified quantifiable signs of retinal degeneration in this Nphp1^tm1Jgg/J mouse model consistent with human SLS. These findings establish phenotypic parameters for future gene therapy studies in this mouse model.

Funding

• Private Foundation Support