NeuroD1 is required for survival of photoreceptors but not pinealocytes: Results from targeted gene deletion studies

Autor: Ochocinska, Margaret J., Muñoz, Estela Maris, Veleri, Shobi, Weller, Joan L., Coon, Steven L., Pozdeyev, Nikita, Iuvone, P. Michael, Goebbels, Sandra, Furukawa, Takahisa, Klein, David C.
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Popis: NeuroD1 encodes a basic helix-loop-helix transcription factor involved in the development of neural and endocrine structures, including the retina and pineal gland. To determine the effect of NeuroD1 knockout in these tissues, a Cre/loxP recombination strategy was used to target a NeuroD1 floxed gene and generate NeuroD1 conditional knockout (cKO) mice. Tissue specificity was conferred using Cre recombinase expressed under the control of the promoter of Crx, which is selectively expressed in the pineal gland and retina. At 2 months of age, NeuroD1 cKO retinas have a dramatic reduction in rod- and cone-driven electroretinograms and contain shortened and disorganized outer segments; by 4 months, NeuroD1 cKO retinas are devoid of photoreceptors. In contrast, the NeuroD1 cKO pineal gland appears histologically normal. Microarray analysis of 2-month-old NeuroD1 cKO retina and pineal gland identified a subset of genes that were affected 2-100-fold; in addition, a small group of genes exhibit altered differential night/day expression. Included in the down-regulated genes are Aipl1, which is necessary to prevent retinal degeneration, and Ankrd33, whose protein product is selectively expressed in the outer segments. These findings suggest that NeuroD1 may act through Aipl1 and other genes to maintain photoreceptor homeostasis. Fil: Ochocinska, Margaret J.. National Instituto of Child Health & Human Development; Estados Unidos Fil: Muñoz, Estela Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Veleri, Shobi. National Institutes of Health; Estados Unidos Fil: Weller, Joan L.. National Instituto of Child Health & Human Development; Estados Unidos Fil: Coon, Steven L.. National Instituto of Child Health & Human Development; Estados Unidos Fil: Pozdeyev, Nikita. University of Emory; Estados Unidos Fil: Iuvone, P. Michael. University of Emory; Estados Unidos Fil: Goebbels, Sandra. Max Planck Institute of Experimental Medicine; Alemania Fil: Furukawa, Takahisa. Osaka University; Japón Fil: Klein, David C.. National Instituto of Child Health & Human Development; Estados Unidos
Databáze: OpenAIRE