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Roger Janz, Xiaoqin Liu, Sumanth Punuru, Ruth Heidelberger; Inactivation of syntaxin 3B in rod photoreceptors causes photoreceptor degeneration.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6047.
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© ARVO (1962-2015); The Authors (2016-present)
In ribbon synapses of the vertebrate retina syntaxin 3B, a retina specific spliceform of the syntaxin 3 gene, is thought to mediate the fusion of synaptic vesicles (Curtis et al. 2010, Datta et al. 2017). Besides its role in synaptic vesicle exocytosis, Syntaxin 3B has also been implicated in trafficking of essential membrane proteins into the outer segments of photoreceptors (Chuang 2007, Mazelova 2009, Zulliger 2015). In order to investigate the role of syntaxin 3B in rod photoreceptors, we have generated conditional syntaxin 3 knockout mice and analyzed the effect of the inactivation of syntaxin 3 on rod photoreceptors.
A cre dependent conditional syntaxin 3 knockout mouse line (obtained from Dr. R. Adachi, MD Anderson Cancer Center Houston) was crossed with a line expressing optimized iCre under the control of the Rhodopsin promoter (Li et al., 2005). Retina sections from conditional knockout mice (Rho-iCre/STX3 fl/fl) and matched control mice (Rho-iCre and STX3 fl/fl) where analyzed by immuno-histology using specific antibodies at 4 weeks and 9 month of age.
In the conditional knockout mice syntaxin 3 was not detectable in photoreceptor cells after 4 weeks of age, demonstrating the efficient inactivation of the gene. Photoreceptor cells in the knockout mice had started to degenerate at 4 weeks of age, and only a single layer of photoreceptors made up of cone photoreceptor cells remained at 9 months of age. Rhodopsin levels were strongly reduced in the outer segments of the mutant mice after 4 weeks, and no rhodopsin was detectable after 9 month.
Rho-Cre/STX3 fl/fl mice did not express syntaxin 3B in the rod photoreceptors, which resulted in their degeneration. The trafficking of rhodopsin to the outer segments was strongly affected by the loss of syntaxin 3B. This indicates that syntaxin 3 is an essential component for the survival of photoreceptors and the trafficking of rhodopsin to the outer segments.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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