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

doi:10.1167/iovs.06-1477

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Gene expression analysis of photoreceptor cell loss in bbs4-knockout mice reveals an early stress gene response and photoreceptor cell damage

Journal article

Peer reviewed

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 and Val C Sheffield

Investigative ophthalmology & visual science, Vol.48(7), pp.3329-3340

07/2007

DOI: 10.1167/iovs.06-1477

PMID: 17591906

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Abstract

To identify and characterize gene expression changes associated with photoreceptor cell loss in a Bbs4-knockout mouse model of retinal degeneration. 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. 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. 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.

Apoptosis

Oncogene Proteins - genetics

Bardet-Biedl Syndrome - metabolism

Microtubule-Associated Proteins - genetics

Oligonucleotide Array Sequence Analysis

Gene Expression Profiling

Acute-Phase Proteins - genetics

Retinal Degeneration - metabolism

Lipocalins

Bardet-Biedl Syndrome - pathology

Endothelin-2 - genetics

Bardet-Biedl Syndrome - genetics

In Situ Nick-End Labeling

Serpins - genetics

Retinal Degeneration - genetics

Mice, Inbred C57BL

Gene Expression Regulation

Suppressor of Cytokine Signaling Proteins - genetics

Mice, Knockout

Suppressor of Cytokine Signaling 3 Protein

Blotting, Northern

Animals

Lipocalin-2

Mice

Photoreceptor Cells, Vertebrate - metabolism

Retinal Degeneration - pathology

Photoreceptor Cells, Vertebrate - pathology

Details

Title: Subtitle: Gene expression analysis of photoreceptor cell loss in bbs4-knockout mice reveals an early stress gene response and photoreceptor cell damage
Creators: Ruth E Swiderski - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA
Darryl Y Nishimura
Robert F Mullins
Marissa A Olvera
Jean L Ross - University of Iowa
Jian Huang
Edwin M Stone
Val C Sheffield
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.48(7), pp.3329-3340
DOI: 10.1167/iovs.06-1477
PMID: 17591906
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: P50-HL-55006 / NHLBI NIH HHS R01-EY-11298 / NEI NIH HHS
Language: English
Date published: 07/2007
Academic Unit: Statistics and Actuarial Science; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980074202771

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