Kidney Week

Abstract: FR-PO0078

Phenotypic Characterization of Embryonic Kidneys in an Ahi1 Knockout Mouse Model of Joubert Syndrome

Session Information

• ADPKD and Cystic Kidney Disease - 2
  October 23, 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

• Turner, Jamie L., Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

Jamie L. Turner

• Cunanan, Joanna, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

Joanna Cunanan, MS

• Rugolo, Francesco, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

Francesco Rugolo, PhD

• Barua, Moumita, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

Moumita Barua, MD

Background

Variants in AHI1 are a common cause of Joubert syndrome (JS) with kidney involvement. JS is a rare, genetically heterogeneous autosomal recessive disorder caused by defects to a sensory organelle called the primary cilium. AHI1 is a primary cilium-located protein expressed during development and adulthood in the kidney. Previous research indicates that AHI1 facilitates canonical Wnt signalling and is involved in cell processes like ciliary trafficking. Expression patterns and specific mechanisms of AHI1’s role in kidney development and disease have scarcely been investigated despite kidney disease being a frequent cause of mortality in JS.

Methods

B6.129(Cg)-Ahi1^tm1Jgg/J wild-type (WT) and knockout (KO) (Ahi^-/-) mouse embryos at embryonic day (E)11.5 and E16.5 were extracted, formalin-fixed paraffin-embedded, sliced in 4 μm sections, stained with hematoxylin and eosin (H&E), and imaged at 40x magnification. Initial inquiry into AHI1 expression across renal cell populations was assessed using the Kidney Interactive Transcriptomics (KIT; https://www.humphreyslab.com/SingleCell/) analyzer on cells and nuclei derived from healthy adult human (GSE118184) and mouse (GSE119531) kidney tissue.

Results

Ahi1^-/- pups exhibited high embryonic and postnatal mortality, with none surviving past 10 days old. By contrast, the recorded Mendelian ratio at E11.5 and E16.5 is consistent with the expected 1:2:1. Preliminary histological investigation of Ahi1^-/- kidneys at E16.5 revealed cysts and tubular dilation up to 126 μm in diameter. In the KIT analyzer, AHI1 expression trended higher towards the distal portion of the nephron (distal convoluted tubule, connecting tubule, and principal cells in the collecting duct) as well as podocytes.

Conclusion

Ahi1 is an important gene for development with KO resulting in structural abnormalities evident by E16.5 and mortality within the first week of life. Preliminary expression analyses support enrichment of AHI1 in specific renal cell populations. Immediate future work will focus on characterizing gene expression during development through bulk and single-nucleus RNA sequencing of whole WT and Ahi1^-/- kidneys to identify molecular drivers of the observed phenotype in this orphan disease and to further define Ahi1 expression patterns along the nephron.

Funding

• Private Foundation Support