Pofut2-KO Mouse

Pofut2, also known as FUT13, is an enzyme that catalyzes protein O-fucosylation on serine/threonine residues of thrombospondin type 1 repeats (TSR) [1,2]. This post-translational modification is essential for proper development in mice, with Pofut2-deficient mouse embryos showing early embryonic lethality [1,3]. It is involved in extracellular matrix (ECM) remodeling and signaling pathways, which are crucial for bone development and other biological processes [3].

Mouse models with Pofut2 knockout (KO) or conditional knockout (CKO) have provided key insights. Deletion of Pofut2 in the developing limb mesenchyme using Prrx1-Cre recombinase led to limb, long bone, and tendon shortening, along with joint stiffness, resembling human and mouse musculoskeletal dysplasias. This was due to decreased BMP and IHH signaling, increased TGF-β signaling, and abnormal ECM properties [3]. In HEK293T cells, CRISPR-Cas9-mediated knockout of POFUT2 blocked secretion of ADAMTS9, and similar gastrulation defects were observed in Pofut2 and Adamts9 knockout embryos, suggesting that defects in ADAMTS9 secretion may be responsible for the gastrulation defects in Pofut2 mutants [4].

In conclusion, Pofut2 is essential for proper development, mainly through its role in O-fucosylation of TSR-containing proteins, which impacts ECM remodeling and signaling. KO and CKO mouse models have been instrumental in uncovering its role in processes like bone development and gastrulation, potentially providing insights into related human diseases such as musculoskeletal dysplasias [3,4].