title: 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(+/-) mouse 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 RGCs are significantly reduced in retinal ganglion cell layer in Bst(+/-) mouse, melanopsin(+) RGCs, also called ipRGCs, appear to be unchanged. Pupillary light reflex 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 electron microscopy in RGC and found that mitochondria morphology was deformed, having irregular borders and lacking cristae. The complex activities of the mitochondrial electron transport chain were significantly decreased. Finally, for subretinal vascularization, we also found that angiogenesis is delayed in Bst(+/-) associated with delayed hyaloid regression. Characterization of Bst(+/-) retina suggests that the Bst(+/-) mouse strain could be a useful murine model. It might be used to explore further the pathogenesis and strategy of treatment of retinal degenerative diseases by employing stem cell technology.
authors.affiliation: Department of Pediatrics, Division of Human Genetics, University of California, Irvine, CA 92697, USA.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Riazifar
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Guoli
authors.initials: G
authors.lastname: Sun
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Johns Hopkins University, Department of Biology, Baltimore, MD 21218, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Rupp
authors.affiliation: Vision Science Group, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Vemaraju
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Fred N
authors.initials: FN
authors.lastname: Ross-Cisneros
authors.affiliation: Vision Science Group, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
authors.affiliation: Johns Hopkins University, Department of Biology, Baltimore, MD 21218, USA.
authors.forename: Samer
authors.initials: S
authors.lastname: Hattar
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
authors.affiliation: Department of Pediatrics, Division of Human Genetics, University of California, Irvine, CA 92697, USA Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA Taosheng.Huang@cchmc.org.
authors.forename: Taosheng
authors.initials: T
authors.lastname: Huang
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010101:Oxygen Consumption; D010641:Phenotype; D012160:Retina / Q000473:pathology* / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D017299:Rod Opsins / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000378:metabolism; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D050819:Transcription Factor Brn-3A; D000099210:Melanopsin; C494189:Pou4f1 protein, mouse
keywords: Bst; Melanopsin; Retinal ganglion cell