BETA2/NeuroD1 null mice: A new model for transcription factor-dependent photoreceptor degeneration

Mark E. Pennesi, Jang Hyeon Cho, Zhuo Yang, Schonmei H. Wu, Jian Zhang, Samuel M. Wu, Ming Jer Tsai

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

BETA2/NeuroD1 is a basic helix-loop-helix transcription factor that is expressed widely throughout the developing nervous system. Previous studies have shown that BETA2/NeuroD1 influences the fate of retinal cells in culture. To analyze the effect of BETA2/NeuroD1 on the structure and function of the retina, we examined a line of BETA2/NeuroD1 knock-out mice that survives until adulthood. At 2-3 months of age, homozygous null mice showed a 50% reduction in rod-driven electroretinograms (ERGs) and a 65% reduction in cone-driven ERGs. ERGs measured from knock-out mice that were >9 months of age were undetectable. At 2-3 months, the number of photoreceptors in the outer nuclear layer was reduced by 50%. In addition, electron microscopy showed that the surviving photoreceptors had shortened outer segments. The number of cones labeled by peanut agglutinin was decreased 50-60%. By 18 months, retinas from null mice were completely devoid of photoreceptors. There appeared to be few changes in the inner retina, although BETA2/NeuroD1 is expressed in this area. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining revealed a dramatic increase in cell death, peaking at approximately postnatal day 3 and continuing into adulthood. No defects in cellbirth were detected using bromodeoxyuridine staining. Our results reveal that BETA2/NeuroD1 not only plays an important role in terminal differentiation of photoreceptors but also serves as a potential survival factor. Loss of BETA2/NeuroD1 results in an age-related degeneration of both rods and cones.

Original languageEnglish (US)
Pages (from-to)453-461
Number of pages9
JournalJournal of Neuroscience
Volume23
Issue number2
StatePublished - Jan 15 2003

Keywords

  • BETA2
  • BETA2/NeuroD1
  • Degeneration
  • Development
  • Differentiation
  • Electroretinogram
  • NeuroD
  • NeuroD1
  • Photoreceptor
  • Retina
  • bHLH

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Pennesi, M. E., Cho, J. H., Yang, Z., Wu, S. H., Zhang, J., Wu, S. M., & Tsai, M. J. (2003). BETA2/NeuroD1 null mice: A new model for transcription factor-dependent photoreceptor degeneration. Journal of Neuroscience, 23(2), 453-461.