A novel mouse model of cholesteryl ester storage disorder with Lipa exon 8 splicing junction mutation
5 affiliations
- 1Department of Clinical Laboratory Medicine, National Center for Child Health and Development
- 2Department of Systems BioMedicine, National Research Institute for Child Health and Development
- 3Laboratory for Biomaterials and Bioengineering (LBB), Institute of Science Tokyo
- 4Department of Pediatrics, and Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University
- 5Department of Pediatrics, Graduate School of Medicine, Osaka Metropolitan University
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.
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BibTeX
@article{mashima2026novel,
title = {{A novel mouse model of cholesteryl ester storage disorder with Lipa exon 8 splicing junction mutation}},
author = {Ryuichi Mashima and Shuji Takada and Yoshitaka Miyamoto and Kei Murayama and Takashi Hamazaki},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-63288-3},
url = {https://doi.org/10.1038/s41598-026-63288-3},
note = {CC BY},
}
RIS
TY - JOUR
TI - A novel mouse model of cholesteryl ester storage disorder with Lipa exon 8 splicing junction mutation
AU - Ryuichi Mashima
AU - Shuji Takada
AU - Yoshitaka Miyamoto
AU - Kei Murayama
AU - Takashi Hamazaki
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-63288-3
UR - https://doi.org/10.1038/s41598-026-63288-3
AB - 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.
SN - 2045-2322
ER -