Abstract
Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.
Highlights
Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of glucosylceramidase (GlcCerase; known as glucocerebrosidase), the lysosomal hydrolase that is responsible for the degradation of glucosylceramide (GlcCer) (Vitner et al, 2010a)
-synuclein aggregates have been observed in the brains of mouse models of other LSDs, and case studies and other clinical data suggest a more general link between Parkinson’s disease (PD) and LSDs (Shachar et al, 2011). This suggests that the search for biochemical and cellular pathways that link PD with GD should not be limited exclusively to changes that occur in GD, but rather should include changes that might be common to a variety of animal models of LSDs
In this Commentary, we describe attempts to generate GD animal models
Summary
Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and died soon after birth. Conditional knockout mice that mimic some features of the human disease have become available. We review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD
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