{
  "abstract": "Lysosomal acid lipase deficiency (LAL-D, OMIM #309,900) is caused by a deficiency of enzyme activity of the LIPA gene and is characterized by an accumulation of cholesteryl esters and triglycerides in the body. LAL-D has two disease subtypes with continuum presentation. Wolman disease is a severe type of LAL-D with typical manifestations of hepatosplenomegaly, diarrhea, vomiting, and severe hepatic disorder with short life expectancy. By contrast, cholesteryl ester storage disorder (CESD) is an attenuated disease subtype of LAL-D with abnormal serum lipids and hepatic involvement. For CESD, the most frequently observed genotype involves a splicing junction mutation of exon 8 (c.894G > A; E8SJM). In this study, we have generated a novel mouse model of CESD with Lipa E8SJM found in humans. Mice homozygous for E8SJM showed visceral manifestations such as hepatosteatosis and hepatosplenomegaly with activated macrophages, as was reported in the Lipa null mouse model for Wolman disease. Interestingly, our novel mouse model of CESD with Lipa E8SJM showed almost normal growth, while that with Lipa null alleles led to severe growth retardation. An accumulation of hepatic lipids began at 2 weeks of age in both mouse models before hepatosplenomegaly became apparent at 8 weeks. These results raise the possibility that this novel mouse model could recapitulate the clinical manifestations of CESD with Lipa E8SJM in humans.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Laboratory Medicine, National Center for Child Health and Development",
    "Department of Systems BioMedicine, National Research Institute for Child Health and Development",
    "Laboratory for Biomaterials and Bioengineering (LBB), Institute of Science Tokyo",
    "Department of Pediatrics, and Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University",
    "Department of Pediatrics, Graduate School of Medicine, Osaka Metropolitan University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ryuichi Mashima"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuji Takada"
    },
    {
      "affs": [
        2
      ],
      "name": "Yoshitaka Miyamoto"
    },
    {
      "affs": [
        3
      ],
      "name": "Kei Murayama"
    },
    {
      "affs": [
        4
      ],
      "name": "Takashi Hamazaki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8vvzxr4phgn34.bib",
  "cited_by": 1,
  "doi": "10.1038/s41598-026-63288-3",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-63288-3",
  "id": "8vvzxr4phgn34",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-63288-3",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2737|Lysosomal Storage Disorders Research"
    ]
  ],
  "openalex": "W7170069736",
  "pdf_url": "https://www.nature.com/articles/s41598-026-63288-3_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/8vvzxr4phgn34.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:58Z",
      "native_id": "ab3a717394ff480494bc75553c488027",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-63288-3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Lysosomal Storage Disorders Research",
      "subfield": "physiology"
    }
  ],
  "title": "A novel mouse model of cholesteryl ester storage disorder with Lipa exon 8 splicing junction mutation",
  "title_text": "A novel mouse model of cholesteryl ester storage disorder with Lipa exon 8 splicing junction mutation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:58Z",
  "url": "https://research.draconitic.com/paper/8vvzxr4phgn34",
  "venue": "Scientific Reports",
  "versions": []
}