Fam161a-flox Mouse

Fam161a, a gene of unknown initial function, encodes a centrosomal-ciliary protein. It is essential for the structure of the photoreceptor connecting cilium (CC) [1]. It binds directly to microtubules, increases the acetylation of α -tubulin, and is part of microtubule -organizing centers, associating with the intracellular microtubule network. Its C -terminal UPF0564 domain mediates microtubule association and interactions with ciliopathy -associated proteins [1].

In Fam161a -deficient mice, visual acuity and electroretinographic responses gradually decrease, and the whole retina thins as shown by optical coherence tomography. Photoreceptor outer segment disks are disorganized, and molecular degenerative markers appear early. These phenotypes indicate that Fam161a deficiency affects retinal function and causes retinal degeneration [3]. Gene augmentation therapy in these knockout mice using an adeno -associated virus encoding the longer mFam161a transcript shows significant structural and functional rescue of photoreceptors [4]. Fine -tuning the gene augmentation therapy, such as using the weak FCBR1 -F0.4 promoter and both human isoforms, enables precise Fam161a expression in the CC and enhances retinal function [2].

In conclusion, Fam161a is crucial for the structure and function of photoreceptor connecting cilia, mainly through its role in microtubule -based cellular processes in the retina. The study of Fam161a knockout mouse models has significantly contributed to understanding its role in retinal degeneration and developing gene -based therapies for retinitis pigmentosa -type 28 caused by bi -allelic null mutations in Fam161a [1,2,3,4].