Pmm2-flox Mouse

PMM2, encoding phosphomannomutase 2, is crucial for the conversion of Man-6-P to Man-1-P. This reaction is essential for the synthesis of guanosine 5'-diphospho-D-mannose, a key nucleotide-activated sugar in constructing protein oligosaccharide chains, thus being involved in protein glycosylation pathways [1].

Mutations in PMM2 cause phosphomannomutase 2 deficiency (PMM2-CDG), the most common N-linked glycosylation disorder [2]. PMM2-CDG patients display a multisystem phenotype, including central nervous system involvement, hepatopathy, and renal abnormalities [2]. In vitro neural models of PMM2-CDG show aberrant neural activity, impaired protein glycosylation, mitochondrial structure, and abnormal glucose metabolism [3]. There is an ongoing search for treatments, including strategies to increase Man-1-P levels, use of mannose derivates, enzyme inhibitors, or repurposed drugs to boost GDP-Man synthesis [1]. A CRISPR-Cas9-generated HepG2 PMM2-CDG knockout model recapitulates the disease phenotype, useful for studying new PMM2 clinical variants and evaluating therapies [4].

In conclusion, PMM2 is vital for protein glycosylation through its role in the synthesis of an essential sugar for oligosaccharide chain construction. Studies on PMM2-CDG, including those using knockout models, have revealed its significance in various biological processes and disease conditions, providing insights into potential therapeutic strategies for this disorder.