Genetic disruption of bassoon in two mutant mouse lines causes divergent retinal phenotypes. Issue 5 (3rd April 2021)

• Record Type: Journal Article
• Authors: Ryl, Miriam; Urbasik, Alexander; Gierke, Kaspar; Babai, Norbert; Joachimsthaler, Anneka; Feigenspan, Andreas; Frischknecht, Renato; Stallwitz, Nina; Fejtová, Anna; Kremers, Jan; von Wittgenstein, Julia; Brandstätter, Johann Helmut
• Is Part Of: FASEB journal. Volume 35:Issue 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-04-03
• Subjects: active zone -- bassoon -- photoreceptor -- photoreceptor death -- ribbon synapse; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202001962R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Bassoon (BSN) is a presynaptic cytomatrix protein ubiquitously present at chemical synapses of the central nervous system, where it regulates synaptic vesicle replenishment and organizes voltage‐gated Ca 2+ channels. In sensory photoreceptor synapses, BSN additionally plays a decisive role in anchoring the synaptic ribbon, a presynaptic organelle and functional extension of the active zone, to the presynaptic membrane. In this study, we functionally and structurally analyzed two mutant mouse lines with a genetic disruption of Bsn — Bsn gt and Bsn ko —using electrophysiology and high‐resolution microscopy. In both Bsn mutant mouse lines, full‐length BSN was abolished, and photoreceptor synaptic function was similarly impaired, yet synapse structure was more severely affected in Bsn gt/gt than in Bsn ko/ko photoreceptors. The synaptic defects in Bsn gt/gt retina coincide with remodeling of the outer retina—rod bipolar and horizontal cell sprouting, formation of ectopic ribbon synaptic sites—and death of cone photoreceptors, processes that did not occur in Bsn ko/ko retina. An analysis of Bsn gt/ko hybrid mice revealed that the divergent retinal phenotypes of Bsn gt/gt and Bsn ko/ko mice can be attributed to the expression of the Bsn gt allele, which triggers cone photoreceptor death and neurite sprouting in the outer retina. These findings shed new light on the existing Bsn mutant mouse models and might help to understand mechanisms that drive photoreceptor death.