Nans-flox Mouse

NANS, encoding the synthase for N-acetylneuraminic acid (sialic acid), is essential in the de novo sialic acid synthesis pathway. Sialic acid at the end of glycoconjugates is crucial for biological processes like brain and skeletal development [1,3].

In humans, biallelic mutations in NANS lead to NANS-CDG, a congenital disorder of glycosylation. Patients show features such as intellectual developmental disorder, facial dysmorphisms, neurologic impairment, short stature, and skeletal dysplasia [1,2]. Knockdown of nansa in zebrafish embryos results in abnormal skeletal development, and exogenous sialic acid partially rescues this phenotype, indicating NANS-mediated sialic acid synthesis is required for early brain and skeletal development [3]. In human cortical organoids, NANS mutation leads to absence of sialic acid and protein polysialylation, reduced neural progenitor proliferation, and disrupted neural migration, differentiation, synapse formation, and neuronal activity [4].

In conclusion, NANS is vital for sialic acid synthesis, which is crucial for brain and skeletal development. Studies on NANS-related models, like zebrafish knockdown and human organoids with NANS mutation, have enhanced our understanding of its role in these processes and in the disease NANS-CDG [1-3,6].