Nme5-flox Mouse

Nme5, a member of the NDPK-like molecules gene family, is associated with ciliary function [1,2]. It encodes a protein that is part of the radial spoke (RS) neck in cilia [2]. Nme5 may also be involved in the regulation of apoptosis, cell cycle, and gemcitabine resistance in pancreatic cancer cells, and it may function in a nuclear factor kappaB (NF-κB)-dependent manner [3].

Nme5-/-knockout mice exhibit doming of the skull, hydrocephalus, and sperm flagellar defects, indicating its importance in ciliary-related functions in vivo [1]. In humans, a homozygous nonsense variant in Nme5 causes primary ciliary dyskinesia (PCD) with radial spoke defects, and morpholino knockdown of nme5 in zebrafish embryos results in motile cilia defects compatible with ciliopathy [2]. Also, in an Alaskan Malamute family, a frameshift variant in Nme5 was associated with PCD, and immunohistochemistry demonstrated absence of the NME5 protein from nasal epithelia of an affected dog [1].

In conclusion, Nme5 is crucial for ciliary function as revealed by gene knockout models in mice and knockdown experiments in zebrafish. These models have contributed to understanding its role in PCD in both humans and dogs, highlighting its significance in ciliary-related disease areas.