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α-Gal antigen-deficient rabbits with GGTA1 gene disruption via CRISPR/Cas9
- Source :
- BMC Genomic Data, Vol 23, Iss 1, Pp 1-10 (2022)
- Publication Year :
- 2022
- Publisher :
- BMC, 2022.
-
Abstract
- Abstract Background Previous studies have identified the carbohydrate epitope Galα1–3Galβ1–4GlcNAc-R (termed the α-galactosyl epitope), known as the α-Gal antigen as the primary xenoantigen recognized by the human immune system. The α-Gal antigen is regulated by galactosyltransferase (GGTA1), and α-Gal antigen-deficient mice have been widely used in xenoimmunological studies, as well as for the immunogenic risk evaluation of animal-derived medical devices. The objective of this study was to develop α-Gal antigen-deficient rabbits by GGTA1 gene editing with the CRISPR/Cas9 system. Results The mutation efficiency of GGTA1 gene-editing in rabbits was as high as 92.3% in F0 pups. Phenotype analysis showed that the α-Gal antigen expression in the major organs of F0 rabbits was decreased by more than 99.96% compared with that in wild-type (WT) rabbits, and the specific anti-Gal IgG and IgM antibody levels in F1 rabbits increased with increasing age, peaking at approximately 5 or 6 months. Further study showed that GGTA1 gene expression in F2-edited rabbits was dramatically reduced compared to that in WT rabbits. Conclusions α-Gal antigen-deficient rabbits were successfully generated by GGTA1 gene editing via the CRISPR/Cas9 system in this study. The feasibility of using these α-Gal antigen-deficient rabbits for the in situ implantation and residual immunogenic risk evaluation of animal tissue-derived medical devices was also preliminarily confirmed.
Details
- Language :
- English
- ISSN :
- 27306844
- Volume :
- 23
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- BMC Genomic Data
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.93d14a5526be4ed59b3d75bfebbc29e2
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12863-022-01068-4