AI Article Synopsis
- Gaucher disease (GD) is a genetic disorder caused by mutations in the GBA gene that affects macrophage function.
- CRISPR gene editing was used to correct the GBA mutation in stem cells, producing cell lines with different genetic variations (homozygous and heterozygous).
- The corrected macrophages demonstrated improved functions, indicating that GD mutations impact their ability to fight infections, and research suggests that having GD may offer some protection against tuberculosis.
Article Abstract
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase (GCase) GBA gene, which result in macrophage dysfunction. CRISPR (clustered regularly interspaced short palindromic repeats) editing of the homozygous L444P (1448T→C) GBA mutation in type 2 GD (GBA-/-) human-induced pluripotent stem cells (hiPSCs) yielded both heterozygous (GBA+/-) and homozygous (GBA+/+) isogenic lines. Macrophages derived from GBA-/-, GBA+/- and GBA+/+ hiPSCs showed that GBA mutation correction restores normal macrophage functions: GCase activity, motility, and phagocytosis. Furthermore, infection of GBA-/-, GBA+/- and GBA+/+ macrophages with the Mycobacterium tuberculosis H37Rv strain showed that impaired mobility and phagocytic activity were correlated with reduced levels of bacterial engulfment and replication suggesting that GD may be protective against tuberculosis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686692 | PMC |
| http://dx.doi.org/10.1093/infdis/jiad141 | DOI Listing |
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