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

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

Research output: Contribution to journalArticle

91 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Retina
Transcription Factors
Knockout Mice
Staining and Labeling
Peanut Agglutinin
Basic Helix-Loop-Helix Transcription Factors
Uridine Triphosphate
DNA Nucleotidylexotransferase
Bromodeoxyuridine
Nervous System
Electron Microscopy
Cell Death
Cell Culture Techniques
Cone-Rod Dystrophies

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pennesi, M., 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.

BETA2/NeuroD1 null mice : A new model for transcription factor-dependent photoreceptor degeneration. / Pennesi, Mark; Cho, Jang Hyeon; Yang, Zhuo; Wu, Schonmei H.; Zhang, Jian; Wu, Samuel M.; Tsai, Ming Jer.

In: Journal of Neuroscience, Vol. 23, No. 2, 15.01.2003, p. 453-461.

Research output: Contribution to journalArticle

Pennesi, M, Cho, JH, Yang, Z, Wu, SH, Zhang, J, Wu, SM & Tsai, MJ 2003, 'BETA2/NeuroD1 null mice: A new model for transcription factor-dependent photoreceptor degeneration', Journal of Neuroscience, vol. 23, no. 2, pp. 453-461.
Pennesi, Mark ; Cho, Jang Hyeon ; Yang, Zhuo ; Wu, Schonmei H. ; Zhang, Jian ; Wu, Samuel M. ; Tsai, Ming Jer. / BETA2/NeuroD1 null mice : A new model for transcription factor-dependent photoreceptor degeneration. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 2. pp. 453-461.
@article{081ba23e5fd2417da60a1497620649ee,
title = "BETA2/NeuroD1 null mice: A new model for transcription factor-dependent photoreceptor degeneration",
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.",
keywords = "BETA2, BETA2/NeuroD1, bHLH, Degeneration, Development, Differentiation, Electroretinogram, NeuroD, NeuroD1, Photoreceptor, Retina",
author = "Mark Pennesi and Cho, {Jang Hyeon} and Zhuo Yang and Wu, {Schonmei H.} and Jian Zhang and Wu, {Samuel M.} and Tsai, {Ming Jer}",
year = "2003",
month = "1",
day = "15",
language = "English (US)",
volume = "23",
pages = "453--461",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "2",

}

TY - JOUR

T1 - BETA2/NeuroD1 null mice

T2 - A new model for transcription factor-dependent photoreceptor degeneration

AU - Pennesi, Mark

AU - Cho, Jang Hyeon

AU - Yang, Zhuo

AU - Wu, Schonmei H.

AU - Zhang, Jian

AU - Wu, Samuel M.

AU - Tsai, Ming Jer

PY - 2003/1/15

Y1 - 2003/1/15

N2 - 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.

AB - 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.

KW - BETA2

KW - BETA2/NeuroD1

KW - bHLH

KW - Degeneration

KW - Development

KW - Differentiation

KW - Electroretinogram

KW - NeuroD

KW - NeuroD1

KW - Photoreceptor

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=0037439739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037439739&partnerID=8YFLogxK

M3 - Article

C2 - 12533605

AN - SCOPUS:0037439739

VL - 23

SP - 453

EP - 461

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 2

ER -