LIPA c.894G>A: From Patients to Models
A study recently accepted for publication in Scientific Reports describes the first mouse model carrying the LIPA c.894G>A (E8SJM) mutation, the most common genetic variant associated with the later-onset form of Lysosomal Acid Lipase Deficiency (LAL-D).
Until now, most animal models used in LAL-D research have been based on complete loss of LAL activity, reflecting the most severe forms of the disease. This newly developed model incorporates the same mutation found in many individuals with later-onset LAL-D, providing a more representative tool to study disease mechanisms and progression.
Researchers observed hepatic accumulation of cholesterol and triglycerides from an early age, together with liver steatosis, hepatomegaly, splenomegaly, macrophage activation and progressive liver fibrosis. Importantly, these mice maintained near-normal growth, better reflecting the clinical presentation seen in many patients with later-onset LAL-D.
One of the study’s most relevant findings is that lipid accumulation appeared before overt organ enlargement became evident, further emphasizing the importance of early diagnosis and timely detection strategies.
While this research does not introduce a new treatment, it provides an important platform for advancing our understanding of LAL-D and for evaluating future therapeutic approaches, including gene therapies and other strategies targeting defects in the LIPA gene.
Reference:
Mashima R., Takada S., Miyamoto Y. et al. A novel mouse model of cholesteryl ester storage disorder with Lipa exon 8 splicing junction mutation. Scientific Reports (2026).
