Dietary phosphorus restriction enables multigenerational breeding of α-Klotho-deficient rats

Authors

Sarai, C., Totsuka, Y., Horii, T., Tamura, S., Gouda, E., Kojima, S., Kouki, T., Ohno, N., Yoshiki, A., Ohmori, T., Kurosu, H., Endo, H., Tominaga, K., Hatada, I., Yamamoto, T., Kuro-o, M., Nagao, Y.

Abstract

Severe -Klotho deficiency causes early mortality and reproductive impairment, limiting the maintenance and physiological analysis of rat models. We generated rats carrying a CRISPR/Cas9-mediated -Klotho deletion spanning exons 1-5 and evaluated dietary phosphorus restriction primarily in the Wistar-Imamichi background. Maternal low-phosphorus (LP) feeding from mating through lactation was associated with higher overall survival to weaning (92.6% versus 85.8% under normal-phosphorus conditions) and a higher proportion of KO animals among weaned survivors (34/113 versus 23/145). Maternal LP feeding also reduced plasma phosphorus in KO pups. Continued LP feeding after weaning supported growth, gonadal development, and natural KO x KO breeding. Across 15 litters, 74 of 85 offspring survived to weaning, and KO colonies were maintained to at least the fifth generation. We additionally characterized 24-h metabolic rhythms in LP-maintained KO animals using indirect calorimetry. These profiles remained heterogeneous under a light-dark cycle. In conclusion, dietary phosphorus restriction provides a reliable strategy for the multigenerational maintenance of severe -Klotho-deficient rats, establishing a maintainable model to investigate residual metabolic and physiological phenotypes.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 19 Oct 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.