| First Author | Formichetti S | Year | 2025 |
| Journal | PLoS Genet | Volume | 21 |
| Issue | 1 | Pages | e1011507 |
| PubMed ID | 39787076 | Mgi Jnum | J:360775 |
| Mgi Id | MGI:7851545 | Doi | 10.1371/journal.pgen.1011507 |
| Citation | Formichetti S, et al. (2025) Genetic gradual reduction of OGT activity unveils the essential role of O-GlcNAc in the mouse embryo. PLoS Genet 21(1):e1011507 |
| abstractText | The reversible glycosylation of nuclear and cytoplasmic proteins (O-GlcNAcylation) is catalyzed by a single enzyme, namely O-GlcNAc transferase (OGT). The mammalian Ogt gene is X-linked, and it is essential for embryonic development and for the viability of proliferating cells. We perturbed OGT's function in vivo by creating a murine allelic series of four single amino acid substitutions, reducing OGT's catalytic activity to a range of degrees. The severity of the embryonic lethality was proportional to the extent of impairment of OGT's catalysis, demonstrating that the O-GlcNAc modification itself is required for early development. We identified hypomorphic Ogt alleles that perturb O-GlcNAc homeostasis while being compatible with embryogenesis. The analysis of the transcriptomes of the mutant embryos at different developmental stages suggested a sexually-dimorphic developmental delay caused by the decrease in O-GlcNAc. Furthermore, a mild reduction of OGT's enzymatic activity was sufficient to loosen the silencing of endogenous retroviruses in vivo. |
