Gene expression analysis of photoreceptor cell loss in Bbs4-knockout mice reveals an early stress gene response and photoreceptor cell damage

Ruth E. Swiderski, Darryl Y. Nishimura, Robert F. Mullins, Marissa A. Olvera, Jean L. Ross, Jian Huang, Edwin M. Stone, Val C. Sheffield

Research output: Journal article publicationJournal articleAcademic researchpeer-review

42 Citations (Scopus)


PURPOSE. To identify and characterize gene expression changes associated with photoreceptor cell loss in a Bbs4-knockout mouse model of retinal degeneration. METHODS. Differential gene expression in the eyes of 5-month-old Bbs4-/- mice undergoing retinal degeneration were analyzed using gene microarrays (Affymetrix, Santa Clara, CA). Elevated ocular transcripts were confirmed by Northern blotting of RNA from Bbs4-/- and three additional mouse models of Bardet-Biedl Syndrome (BBS). TUNEL assays and transmission electron microscopy were used to study cell death and photoreceptor morphology in these mice. RESULTS. Three hundred fifty-four probes were differentially expressed in Bbs4-/- eyes compared with controls using a twofold cutoff. Numerous vision-related transcripts decreased because of photoreceptor cell loss. Increased expression of the stress response genes Edn2, Lcn2, Serpina3n, and Socs3 was noted at 5 months of age and as early as postnatal week 4 in the eyes of four BBS mouse model strains. A burst of apoptotic activity in the photoreceptor outer nuclear layer at postnatal week 2 and highly disorganized outer segments by postnatal weeks 4 to 6 was observed in all four strains. CONCLUSIONS. The specific loss of photoreceptors in Bbs4 -/- mice allows us to identify a set of genes that are preferentially expressed in photoreceptors compared with other cell types found in the eye and is a valuable resource in the continuing search for genes involved in retinal disease. The molecular and morphologic changes observed in young BBS animal model eyes implies that BBS proteins play a critical, early role in establishing the correct structure and function of photoreceptors.
Original languageEnglish
Pages (from-to)3329-3340
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Issue number7
Publication statusPublished - 1 Jul 2007
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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