Animal Models for the Study of Gaucher Disease

Area of Science:

• Biochemistry
• Genetics
• Cell Biology

Background:

• Gaucher disease (GD) is a sphingolipidosis caused by mutations in the GBA1 gene, leading to deficient acid β-glucocerebrosidase (GCase) activity.
• Accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in lysosomes, particularly in macrophages, is a hallmark of GD.
• Misfolding of mutant GCase in the endoplasmic reticulum (ER) triggers ER stress and the unfolded protein response (UPR).

Purpose of the Study:

• To review animal models used for studying Gaucher disease.
• To elucidate the molecular and cellular mechanisms underlying GD pathogenesis.
• To understand the role of ER stress and UPR in GD.

Main Methods:

• Review of existing literature on Gaucher disease animal models.
• Analysis of studies investigating GCase enzyme function and protein trafficking.
• Examination of research on ER-associated degradation (ERAD) and unfolded protein response (UPR) in GD.

Main Results:

• Animal models recapitulate key features of GD, including GlcCer accumulation and GCase deficiency.
• Studies highlight the impact of GCase misfolding, ER stress, and ERAD on disease severity.
• GD exhibits significant clinical heterogeneity, with distinct neurological involvement in different types.

Conclusions:

• Animal models are crucial for dissecting the complex pathophysiology of Gaucher disease.
• Understanding ER stress and protein misfolding pathways offers therapeutic targets for GD.
• Further research using these models can improve diagnosis and treatment strategies for GD.