Phenotypic and functional characterization of Bst+/- mouse retina

Abstract

The belly spot and tail (Bst+/-) mouse phenotype is caused by mutations of the ribosomal protein L24 (Rpl24). Among various phenotypes in Bst+/- mice, the most interesting are its retinal abnormalities, consisting of delayed closure of choroid fissures, decreased ganglion cells, and subretinal vascularization. We further characterized the Bst+/- mice and investigated the underlying molecular mechanisms to assess the feasibility of using this strain as a model for stem cell therapy of retinal degenerative diseases due to retinal ganglion cell (RGC) loss. We found that, although RGC are significantly reduced in retinal ganglion cell layer in Bst+/- mouse, melanopsin-positive RGC, also called ipRGCs, appear to be unchanged. Pupillary light reflex (PLR) was completely absent in Bst+/- mice, but they had a normal circadian rhythm. In order to examine the pathological abnormalities in Bst+/- mice, we performed electronic microscopy (EM) in RGC and found that mitochondria morphology was deformed, having irregular borders and lacking cristae. The complex activities of mitochondrial electron transport chain were decreased significantly. Finally, for subretinal vascularization, we also found that angiogenesis is delayed in Bst+/- associated with delayed haloid regression. Characterization of Bst+/- retina suggests that the Bst+/- mouse strain could be a useful murine model, which can be used to further explore the pathogenesis and strategy of treatment of retinal degenerative diseases through employing stem cell technology.