The ovine Type II Gaucher disease model recapitulates aspects of human brain disease.

Winner, Leanne K.; Beard, Helen; Karageorgos, Litsa; Smith, Nicholas J.; Hopwood, John J.; Hemsley, Kim M.

doi:10.1016/j.bbadis.2023.166658

Cited by 2 publications

(1 citation statement)

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“…Purified detergent resistant membranes (DRM; lipid rafts) from the occipital cortex and spleen of affected sheep also showed significant increases in the concentrations of GlcCer, hexosylsphingosine, BMP, and gangliosides and decreases in the percentage of cholesterol and phosphatidylcholine [144]. In a very recent study, pathological changes in GD lamb brain were carefully investigated and compared to those in GD patient post-mortem tissue [145]. Significant expansion of the endo/lysosomal system in GD lamb cingulate gyrus was noted.…”

Section: Ovine Modelmentioning

confidence: 99%

Animal Models for the Study of Gaucher Disease

Cabasso,

Kuppuramalingam,

Lelieveld

et al. 2023

IJMS

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In Gaucher disease (GD), a relatively common sphingolipidosis, the mutant lysosomal enzyme acid β-glucocerebrosidase (GCase), encoded by the GBA1 gene, fails to properly hydrolyze the sphingolipid glucosylceramide (GlcCer) in lysosomes, particularly of tissue macrophages. As a result, GlcCer accumulates, which, to a certain extent, is converted to its deacylated form, glucosylsphingosine (GlcSph), by lysosomal acid ceramidase. The inability of mutant GCase to degrade GlcSph further promotes its accumulation. The amount of mutant GCase in lysosomes depends on the amount of mutant ER enzyme that shuttles to them. In the case of many mutant GCase forms, the enzyme is largely misfolded in the ER. Only a fraction correctly folds and is subsequently trafficked to the lysosomes, while the rest of the misfolded mutant GCase protein undergoes ER-associated degradation (ERAD). The retention of misfolded mutant GCase in the ER induces ER stress, which evokes a stress response known as the unfolded protein response (UPR). GD is remarkably heterogeneous in clinical manifestation, including the variant without CNS involvement (type 1), and acute and subacute neuronopathic variants (types 2 and 3). The present review discusses animal models developed to study the molecular and cellular mechanisms underlying GD.

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Section: Ovine Modelmentioning

confidence: 99%