Mau2-KO Mouse

MAU2, also known as Scc4, is a protein-encoding gene. It forms a heterodimer with NIPBL, and this complex is crucial for loading the cohesin complex onto chromatin [2,4,6,8]. Cohesin is involved in multiple biological processes such as chromatin structure organization, gene regulation, sister chromatid pairing during cell division, DNA repair, and gene transcription and silencing [1,4].

In mouse models, neural crest cell-specific inactivation of Mau2 strongly affects craniofacial development. Surprisingly, early neural crest cell proliferation and migration are only moderately affected. Moreover, Mau2 single homozygous mutants exhibit a more severe craniofacial phenotype compared to Nipbl;Mau2 double homozygous mutants, suggesting that the Mau2/Nipbl interaction may not only be for cohesin loading but also to restrict Nipbl-regulated gene expression [8]. In humans, loss-of-function variants in MAU2 can cause Cornelia de Lange syndrome (CdLS), a rare congenital developmental disorder. A novel MAU2 variant in a Chinese patient with CdLS led to reduced exogenous mutant protein level and potentially impacted the structural stability of the MAU2/NIPBL complex [2,7]. Genome-wide association studies have also associated MAU2 with non-alcoholic fatty liver disease (NAFLD) and identified it as a potential susceptibility locus for HCC [3,5].

In conclusion, MAU2 is essential for loading cohesin onto chromatin, playing a vital role in various biological processes. Studies using mouse models and human patient samples have revealed its significance in craniofacial development and its association with diseases like CdLS, NAFLD, and HCC. These findings enhance our understanding of the biological functions related to MAU2 and the mechanisms underlying these diseases.