Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35661110.
- Also identified by DOI 10.1038/s41467-022-30847-x and PMC identifier 9166810.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD caused by PIGO mutations as well as development of effective gene therapy. As the clinical manifestations of IGD are systemic and lifelong lasting, we treated the mice with adeno-associated virus for homology-independent knock-in as well as extra-chromosomal expression of Pigo cDNA. Significant amelioration of neuronal phenotypes and growth defect was achieved, opening a new avenue for curing IGDs.
Medical subject headings
- Glycosylphosphatidylinositols
- Seizures