Nup85-flox Mouse

Nup85, encoding nucleoporin, is a member of the Y-complex of the nuclear pore complex (NPC). NPC is crucial for nucleocytoplasmic transport, regulation of mitosis, transcription, and chromatin organization [3]. Nup85 may also be involved in lipid metabolism-related pathways as it was shown to interact with C-C motif chemokine receptor 2 (CCR2) and regulate PI3K/AKT signaling pathway in non-alcoholic fatty liver disease (NAFLD) [2].

In disease-related research, Nup85 pathogenic variants have been associated with multiple conditions. In an Italian boy, novel compound heterozygous variants in Nup85 led to steroid-resistant nephrotic syndrome (SRNS) along with severe neurodevelopmental impairment including microcephaly, axial hypotonia, and refractory seizures [1]. In addition, Nup85 variants were reported in patients with primary autosomal recessive microcephaly (MCPH) and Seckel syndrome (SCKS) spectrum disorders without SRNS [3,4]. Mutant Nup85 was associated with a reduced number of NPCs, abnormal mitotic spindle morphology, and decreased cell viability and proliferation in patient cells [4]. In NAFLD, knockdown of Nup85 in a mouse model alleviated fat disorder and inflammation, while its over-expression increased lipid accumulation and inflammation [2].

In summary, Nup85 is essential for the normal function of the nuclear pore complex and is involved in various biological processes. Studies on Nup85-related gene knockout or knockdown models in mice and human patients have revealed its role in diseases such as SRNS, neurodevelopmental disorders, and NAFLD, providing insights into the underlying mechanisms of these diseases [1,2,3,4].