Abstract
Purpose :
SPATA7, an early onset LCA3 retinal disease gene, encodes a putative scaffold protein that is essential for the proper assembly of connecting cilium (CC) complex in the photoreceptor cells. Previous studies show that SPATA7 interacts with other photoreceptor-specific ciliary proteins, such as RPGR and RPGRIP1, and maintains the integrity of CC integrity. However, although it is clear that Spata7 is required for the early formation of the CC, whether it is also required for the maintenance of the CC is not clear. This study aims to elucidate the function of Spata7 in the adult retina.
Methods :
To investigate Spata7 function in the retina at the adult stage, loss of function mutation is induced in the adult retina upon tamoxifen induction of the inducible Spata7 knockout mouse (Spata7flox/-; UbcCreERT2/+). The phenotype of the mutant mice retina is characterized through a combination of histology, immunohistochemistry, and electroretinogram (ERG).
Results :
Spata7 is also essential for maintaining the integrity of the mature retinal CC. Loss of Spata7 in adults causes phenotypes similar to those seen in germline mutant mice, including photoreceptor cell degeneration, defective ERG responses, etc. Close examination of CC reveals that significantly shortened NPHP1 length can be detected when Spata7 is deleted. Consistently, mislocalization of Rhodopsin protein is observed in the outer nuclease layer, which leads to ER stress-mediated apoptosis.
Conclusions :
Our results indicate that Spata7 is not only required for the establishment but also for the maintenance of the CC of the photoreceptors. In addition, the approach used in this study will facilitate achieving a mechanistic understanding of CC architecture and function.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.