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Volume 27
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10.3390/ijms27020716
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Sex-Related Expression of Klotho in Rat Kidneys: Species Differences Between Rats and Mice

by
Davorka Breljak
1,*,
Dean Karaica
1,
Ivana Vrhovac Madunić
1,
Vedran Micek
2,
Tatjana Orct
3,
Marija Ljubojević
1,
Dubravka Rašić
1,
Željka Vogrinc
4,
Saša Kralik
4,
Marko Gerić
1,
Goran Gajski
1,
Ivana Novak Jovanović
1,
Lucia Nanić
1,5,
Jasna Jurasović
3,
Maja Peraica
1,
Ivica Rubelj
5 and
Ivan Sabolić
1
1
Division of Toxicology, Institute for Medical Research and Occupational Health, 10 000 Zagreb, Croatia
2
Laboratory Animals Unit, Institute for Medical Research and Occupational Health, 10 000 Zagreb, Croatia
3
Division of Occupational and Environmental Health, Institute for Medical Research and Occupational Health, 10 000 Zagreb, Croatia
4
Department of Laboratory Diagnostics, University Hospital Centre, 10 000 Zagreb, Croatia
5
Laboratory for Molecular and Cellular Biology, Division of Molecular Biology, Ruđer Bošković Institute, 10 000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(2), 716; https://doi.org/10.3390/ijms27020716 (registering DOI)
Submission received: 15 December 2025 / Revised: 31 December 2025 / Accepted: 7 January 2026 / Published: 10 January 2026
(This article belongs to the Special Issue Current Research in Membrane Transporters, Channels, and Receptors)
Versions Notes

Abstract

The anti-aging gene/protein Klotho (Kl), most present in kidneys, has been well studied in mice (mKl), but not in rats (rKl). This study investigated the renal rKl expression in male and female rats. Sex-related measurement of rKl-controlled electrolytes was performed in plasma/urine samples, as were tests on species differences in renal Kl expression (rats vs. mice). rKl mRNA/protein expression was studied by qRT-PCR/Western-blotting in renal total RNA/cell membranes and its localization by immunofluorescence microscopy. Urine/plasma ions (phosphate/total calcium) and macroelements (phosphorus/calcium) were measured biochemically and by ICP-MS, respectively. In rat kidneys, the rKl mRNA/protein was detected in the cortex, outer and inner stripe but not in the papilla, and was immunolocalized in the basolateral membrane of proximal tubules in the cortex and outer stripe, but not in the intercalating cells of the cortical distal tubules, whereas mKl was observed in the mouse kidney cortex but not the outer stripe. Female-dominant expression of renal rKl, affected by androgen’s inhibitory effect, may have contributed to the sex-related level of urine electrolytes, particularly phosphates. Renal mKl expression was male-dominant. Sex- and species-related differences in renal Kl expression may be relevant for the selection of the sex and/or the model organism in studies addressing aging/mineral homeostasis.
Keywords: distal tubules; kidney; kl/kl mice; inorganic phosphate; membrane-bound Kl; proximal tubules; sexual dimorphism distal tubules; kidney; kl/kl mice; inorganic phosphate; membrane-bound Kl; proximal tubules; sexual dimorphism

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MDPI and ACS Style

Breljak, D.; Karaica, D.; Vrhovac Madunić, I.; Micek, V.; Orct, T.; Ljubojević, M.; Rašić, D.; Vogrinc, Ž.; Kralik, S.; Gerić, M.; et al. Sex-Related Expression of Klotho in Rat Kidneys: Species Differences Between Rats and Mice. Int. J. Mol. Sci. 2026, 27, 716. https://doi.org/10.3390/ijms27020716

AMA Style

Breljak D, Karaica D, Vrhovac Madunić I, Micek V, Orct T, Ljubojević M, Rašić D, Vogrinc Ž, Kralik S, Gerić M, et al. Sex-Related Expression of Klotho in Rat Kidneys: Species Differences Between Rats and Mice. International Journal of Molecular Sciences. 2026; 27(2):716. https://doi.org/10.3390/ijms27020716

Chicago/Turabian Style

Breljak, Davorka, Dean Karaica, Ivana Vrhovac Madunić, Vedran Micek, Tatjana Orct, Marija Ljubojević, Dubravka Rašić, Željka Vogrinc, Saša Kralik, Marko Gerić, and et al. 2026. "Sex-Related Expression of Klotho in Rat Kidneys: Species Differences Between Rats and Mice" International Journal of Molecular Sciences 27, no. 2: 716. https://doi.org/10.3390/ijms27020716

APA Style

Breljak, D., Karaica, D., Vrhovac Madunić, I., Micek, V., Orct, T., Ljubojević, M., Rašić, D., Vogrinc, Ž., Kralik, S., Gerić, M., Gajski, G., Jovanović, I. N., Nanić, L., Jurasović, J., Peraica, M., Rubelj, I., & Sabolić, I. (2026). Sex-Related Expression of Klotho in Rat Kidneys: Species Differences Between Rats and Mice. International Journal of Molecular Sciences, 27(2), 716. https://doi.org/10.3390/ijms27020716

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