Transcriptomics

Dataset Information

0

Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model


ABSTRACT: Gaucher disease, the most prevalent lysosomal storage disease, is caused by homozygous mutations at the GBA gene, which is responsible for encoding the enzyme glucocerebrosidase. Neuronopathic Gaucher disease is associated with microgliosis, astrogliosis, and neurodegeneration. However, the role that microglia, astrocytes, and neurons play in the disease remains to be determined. In the current study, we developed inducible, cell-type specific Gba KO mice to understand the individual impacts of Gba deficiencies on microglia and neurons. Gba was conditionally knocked out either exclusively in microglia or neurons, or throughout the body. These mouse models were developed using a tamoxifen-inducible Cre system, with tamoxifen administration commencing at weaning. Microglia-specific Gba KO mice showed no signs of disease. However, the neuron-specific Gba KO resulted in a shortened lifespan, severe weight loss, and ataxia. These mice also had significant neurodegeneration, microgliosis, and astrogliosis accompanied by the accumulation of glucosylceramide and glucosylsphingosine, recapitulating Gaucher disease-like symptoms. These surprising findings reveal that, unlike the neuron-specific Gba deficiency, microglia-specific Gba deficiency alone does not induce disease. The neuronal Gaucher disease mouse model, with a median survival of 16 weeks, may be useful for future studies of pathogenesis and the evaluation of therapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE247436 | GEO | 2024/10/02

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-02-03 | GSE202929 | GEO
2023-02-03 | GSE202711 | GEO
2020-11-08 | GSE157991 | GEO
2020-11-08 | GSE157987 | GEO
2022-12-31 | GSE190012 | GEO
2022-12-31 | GSE190013 | GEO
2022-11-30 | GSE206368 | GEO
2016-09-27 | PXD001598 | Pride
2022-07-24 | GSE208781 | GEO
2022-07-24 | GSE208783 | GEO