A novel mouse model of cholesteryl ester storage disorder with Lipa exon 8 splicing junction mutation
Year: 2026
Type: article
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.
Source: Scientific Reports
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7170069736