Semi-Lethal Primary Ciliary Dyskinesia in Rats Lacking the Gene.

(non-metastatic cells 7, nucleoside diphosphate kinase 7) is a member of a gene family with a profound effect on health/disease status. NME7 is an established member of the ciliome and contributes to the regulation of the microtubule-organizing center. We aimed to create a rat model to further investigate the phenotypic consequences of gene deletion. The CRISPR/Cas9 nuclease system was used for the generation of Sprague Dawley knock-out rats targeting the exon 4 of the gene. We found the homozygous gene deletion to be semi-lethal, as the majority of SD pups died prior to weaning. The most prominent phenotypes in surviving SD animals were hydrocephalus, situs inversus totalis, postnatal growth retardation, and sterility of both sexes. Thinning of the neocortex was histologically evident at 13.5 day of gestation, dilation of all ventricles was detected at birth, and an external sign of hydrocephalus, i.e., doming of the skull, was usually apparent at 2 weeks of age. Heterozygous SD rats developed normally; we did not detect any symptoms of primary ciliary dyskinesia. The transcriptomic profile of liver and lungs corroborated the histological findings, revealing defects in cell function and viability. In summary, the knock-out of the rat gene resulted in a range of conditions consistent with the presentation of primary ciliary dyskinesia, supporting the previously implicated role of the centrosomally located gene in ciliogenesis and control of ciliary transport.