Gene expression analysis of photoreceptor cell loss in bbs4-knockout mice reveals an early stress gene response and photoreceptor cell damage.
Invest Ophthalmol Vis Sci
; 48(7): 3329-40, 2007 Jul.
Article
en En
| MEDLINE
| ID: mdl-17591906
ABSTRACT
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_congenital_chromosomal_anomalies
Asunto principal:
Degeneración Retiniana
/
Proteínas de Fase Aguda
/
Regulación de la Expresión Génica
/
Células Fotorreceptoras de Vertebrados
/
Síndrome de Bardet-Biedl
/
Proteínas Asociadas a Microtúbulos
Límite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos