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R.E. Swiderski, D.Y. Nishimura, R.F. Mullins, M. Andrews, E.M. Stone, V.C. Sheffield; Gene Expression Analysis of Photoreceptor Cell Loss in a Mouse Model of Bardet Biedl Syndrome 4 (Bbs4) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5248.
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Purpose:Bardet Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive form of retinal degeneration. In addition to retinal degeneration, BBS patients have mental retardation, obesity, renal anomalies, hypogonadism, polydactyly, and an increased incidence of congenital heart disease, diabetes mellitus, and hypertension. To date, eight BBS genes have been identified. We have created a Bbs4 knockout mouse and demonstrated that Bbs4 (–/–) mice undergo progressive retinal degeneration through an apoptotic mechanism that targets the photoreceptor cells. Methods:Differential gene expression in the eyes of 5 month–old Bbs4 (+/+) and Bbs4 (–/–) mice undergoing retinal degeneration were analyzed using Affymetrix Gene Chip mouse genome 430 2.0 microarrays. Results:Of the >39,000 probe sets present on the Affymetrix array, 1345 were differentially expressed in Bbs4(–/–) eyes compared to controls using a 2–fold cutoff. As expected, numerous vision–related transcripts decreased due to photoreceptor cell loss. Expression of all of the known Bbs genes, with the exception of Bbs6, decreased as well. Gene ontology analysis revealed modulation of genes involved in transcription, apoptosis, signaling and extracellular matrix remodeling. Conclusions:The specific loss of photoreceptors in the Bbs4(–/–) mouse allows us to identify a set of genes that are preferentially expressed in photoreceptors compared to other cell types found in the eye. The identification of genes expressed preferentially in photoreceptors may prove valuable in the continuing search for genes involved in inherited retinal disease. Further examination of the differentially expressed genes in the Bbs4 (–/–) mouse eye as well as in other Bbs knockout mice may also offer insight into the mechanism underlying programmed photoreceptor cell death.
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