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Review
. 2024 Feb 3;12(2):362.
doi: 10.3390/biomedicines12020362.

The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease

Ioannis Kofotolios  1   2 , Michael J Bonios  3 , Markos Adamopoulos  2 , Iordanis Mourouzis  4 , Gerasimos Filippatos  5 , John N Boletis  1 , Smaragdi Marinaki  1 , Manolis Mavroidis  2
Affiliations
Review

The Han:SPRD Rat: A Preclinical Model of Polycystic Kidney Disease

Ioannis Kofotolios et al. Biomedicines. .

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) stands as the most prevalent hereditary renal disorder in humans, ultimately culminating in end-stage kidney disease. Animal models carrying mutations associated with polycystic kidney disease have played an important role in the advancement of ADPKD research. The Han:SPRD rat model, carrying an R823W mutation in the Anks6 gene, is characterized by cyst formation and kidney enlargement. The mutated protein, named Samcystin, is localized in cilia of tubular epithelial cells and seems to be involved in cystogenesis. The homozygous Anks6 mutation leads to end-stage renal disease and death, making it a critical factor in kidney development and function. This review explores the utility of the Han:SPRD rat model, highlighting its phenotypic similarity to human ADPKD. Specifically, we discuss its role in preclinical trials and its importance for investigating the pathogenesis of the disease and developing new therapeutic approaches.

Keywords: ADPKD; Han:SPRD rat; PKD/Mhm rat; PKDR1; anks6; ciliopathies; nephronopthisis; polycystic kidney disease.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Characteristics of the kidney in wild-type (A) and Han:SPRD Cy/+ rats (B), hematoxylin and eosin (HE)-stained kidneys of 12-week-old rats (unpublished results, scale bar: 1.5 mm).
Figure 2
Figure 2
Immunohistochemical staining of renal cortex was performed in 12-week-old wild-type (A) and PKD/Mhm (Cy/+) (B) rats for Anks6. Anks6 localized in the brush border of proximal tubules (red arrow). Cysts came mainly from proximal tubules, but there were also cysts without anks6 expression (arrowhead) (unpublished results, the Anti-Anks6 sc-515124 Ab Santa Cruz Biotechnology, was used in a 1:150 dilution; scale bar 100 μm).
Figure 3
Figure 3
Anks6 localizes in the inversin compartment of renal primary cilium and interacts with other nephrocystins in transition zone. The polycystin complex, which acts as a calcium channel, is localized in the primary cilia as well, however a clear interaction with anks6 has not been yet revealed. “Created with BioRender.com, accessed on 26 January 2024”.
See this image and copyright information in PMC

References

    1. Kurschat C.E., Müller R.U., Franke M., Maintz D., Schermer B., Benzing T. An approach to cystic kidney diseases: The clinician’s view. Nat. Rev. Nephrol. 2014;10:687–699. doi: 10.1038/nrneph.2014.173. - DOI - PubMed
    1. Cramer M.T., Guay-Woodford L.M. Cystic Kidney Disease: A Primer. Adv. Chronic Kidney Dis. 2015;22:297–305. doi: 10.1053/j.ackd.2015.04.001. - DOI - PubMed
    1. Rohatgi R. Extra-Renal Manifestations 5. Nephronophthisis (NPHP)-Medullary Cystic Kidney Disease (MCKD) 2008. [(accessed on 31 January 2023)]. Available online: http://pkdb.mayo.edu,
    1. Iglesias C.G., Torres V.E., Offord K.P., Holley K.E., Beard C.M., Kurland L.T. Epidemiology of Adult Polycystic Kidney Disease, Olmsted County, Minnesota: 1935–1980. Am. J. Kidney Dis. 1983;2:630–639. doi: 10.1016/S0272-6386(83)80044-4. - DOI - PubMed
    1. Solazzo A., Testa F., Giovanella S., Busutti M., Furci L., Carrera P., Ferrari M., Ligabue G., Mori G., Leonelli M., et al. The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta-analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition. PloS ONE. 2018;13:e0190430. doi: 10.1371/journal.pone.0190430. - DOI - PMC - PubMed

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