Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.
Ryoko KuwayamaKeiichiro SuzukiJun NakamuraEmi AizawaYoshichika YoshiokaMasahito IkawaShin NabatameKen-Ichi InoueYoshiari ShimmyoKeiichi OzonoTaroh KinoshitaYoshiko MurakamiPublished in: Nature communications (2022)
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.
Keyphrases
- gene therapy
- mouse model
- poor prognosis
- replacement therapy
- cerebral ischemia
- high fat diet induced
- stem cells
- type diabetes
- metabolic syndrome
- sleep quality
- adipose tissue
- dna methylation
- long non coding rna
- gene expression
- brain injury
- physical activity
- bioinformatics analysis
- drug induced
- blood brain barrier
- mesenchymal stem cells
- cell therapy
- genome wide identification
- smoking cessation
- wild type