Nup85-KO Mouse

Nup85, encoding nucleoporin, is a member of the Y-complex of the nuclear pore complex (NPC) crucial for nucleocytoplasmic transport, mitosis regulation, transcription, and chromatin organization [3,4]. It is also related to lipid metabolism and inflammation, potentially interacting with the PI3K/AKT signaling pathway [2].

In humans, Nup85-related disorders have diverse phenotypes. Pathogenic variants in Nup85 can cause steroid-resistant nephrotic syndrome (SRNS), often with associated severe neurodevelopmental impairments such as microcephaly, axial hypotonia, motor milestone delays, and refractory seizures [1]. It has also been linked to primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders without SRNS [3,4]. In a murine non-alcoholic fatty liver disease (NAFLD) model, increased Nup85 expression was associated with fat disorder and inflammation, while knockdown had opposite effects [2]. In macrophages of non-alcoholic steatohepatitis (NASH) mice, Nup85, as a substrate for chaperone-mediated autophagy (CMA), was found to be involved in monocyte recruitment and disease progression [5].

In conclusion, Nup85 is essential for normal physiological functions, especially in the context of kidney and brain development, as well as lipid metabolism and inflammation regulation. Studies of Nup85 in disease models like SRNS, NAFLD, and NASH have provided insights into its role in these disease conditions, highlighting its potential as a therapeutic target.