April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Gene Expression Profile of a New Retinal Mutant with Immature Cone-Like Photoreceptors
Author Affiliations & Notes
  • Debbie F. Cheng
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland
  • Jerome E. Roger
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland
  • Norimoto Gotoh
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland
  • Harsha Rajasimha
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland
  • Matthew Brooks
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland
  • Bo Chang
    The Jackson Laboratory, Bar Harbor, Maine
  • Anand Swaroop
    Neurobiol-Neurodegen & Repair Lab, NEI, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  Debbie F. Cheng, None; Jerome E. Roger, None; Norimoto Gotoh, None; Harsha Rajasimha, None; Matthew Brooks, None; Bo Chang, None; Anand Swaroop, None
  • Footnotes
    Support  NIH/NEI Intramural Funding
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5423. doi:
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      Debbie F. Cheng, Jerome E. Roger, Norimoto Gotoh, Harsha Rajasimha, Matthew Brooks, Bo Chang, Anand Swaroop; Gene Expression Profile of a New Retinal Mutant with Immature Cone-Like Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5423.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Retinal differentiation is regulated by extrinsic and intrinsic factors. Neural Retinal Leucine Zipper (NRL) transcription factor is required for rod differentiation, and a lack of its expression leads to an excess of S cones. This project was undertaken to characterize a new mouse retinal mutant (Nrm) with immature cone-like photoreceptors, with a goal to identify regulatory networks that are upstream of NRL and control photoreceptor fate commitment.

Methods: : RNA-Seq and exome sequencing are being used to generate expression profile and identify the genetic defect in Nrm mutant. RNA of 1 month-old Nrm, wild type (WT) and Nrl-/- mice were sequenced using Genome analyzer IIx from Illumina. Differentially expressed genes (Fold Change 2) were identified and analyzed using Partek genomics suite. Validation was completed through High-Throughput qPCR Taqman Assay.

Results: : A comparative expression analysis of Nrm, WT, and Nrl-/- mice revealed that 3835 genes had a fold change greater than 2 when comparing Nrm and Nrl-/-, 3268 for Nrm and WT, and 3758 for Nrl-/-and WT. Only 734 genes were specifically up or downregulated when comparing Nrm with Nrl-/- and WT. 100 alternatively spliced RNA with FC2 were identified as differentially expressed only in Nrm compared to WT and Nrl-/-. More genes involved in translation regulation were upregulated in Nrm compared to Nrl-/- and WT mice. qPCR confirmed RNA-seq findings that rod transcription factors NRL, NR2E3, RORb and rod visual pathway genes were not expressed. Cone visual pigments were not expressed, yet normal levels of Pde6c, Gnat2 and Cngb3 expression were retained in Nrm mice. Interestingly, expression of Crx, Otx2, and Pax6 did not change in Nrm with respect to Nrl-/- and WT mice. Exome sequencing is in progress.

Conclusions: : The genetic change in Nrm appears to affect a pathway upstream of NRL, leading to a gene expression profile close to Nrl-/-, but with no increase of S- and M-opsins. No marker of mature cones was present, signifying this mutated gene is essential for photoreceptor maturation in addition to rod cell fate.

Keywords: photoreceptors • gene/expression • retinal development 

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