{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Jichi Medical University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "C. Sarai"
    },
    {
      "name": "Y. Totsuka"
    },
    {
      "name": "T. Horii"
    },
    {
      "name": "S. Tamura"
    },
    {
      "name": "E. Gouda"
    },
    {
      "name": "S. Kojima"
    },
    {
      "name": "T. Kouki"
    },
    {
      "name": "N. Ohno"
    },
    {
      "name": "A. Yoshiki"
    },
    {
      "name": "T. Ohmori"
    },
    {
      "name": "H. Kurosu"
    },
    {
      "name": "H. Endo"
    },
    {
      "name": "K. Tominaga"
    },
    {
      "name": "I. Hatada"
    },
    {
      "name": "T. Yamamoto"
    },
    {
      "name": "M. Kuro-o"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Nagao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a971ax2y56jkb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.17.759802",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759802v1.full",
  "id": "a971ax2y56jkb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759802v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "physiology"
    ],
    [
      "openalex",
      "2727|Parathyroid Disorders and Treatments"
    ]
  ],
  "openalex": "W7222896804",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759802v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a971ax2y56jkb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:24Z",
      "native_id": "10.64898/2026.10.17.759802",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759802v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Dietary phosphorus restriction enables multigenerational breeding of α-Klotho-deficient rats",
  "title_text": "Dietary phosphorus restriction enables multigenerational breeding of α-Klotho-deficient rats",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:24Z",
  "url": "https://research.draconitic.com/paper/a971ax2y56jkb",
  "venue": "bioRxiv",
  "versions": []
}