Untranslated element in neurofilament mRNA has neuropathic effect on motor neurons of transgenic mice

Zhenying (Jane) Nie, Junhua Wu, Jinbin Zhai, Hong Lin, Weiwen Ge, William W. Schlaepfer, Rafaela Cañete-Soler

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Studies of experimental motor neuron degeneration attributable to expression of neurofilament light chain (NF-L) transgenes have raised the possibility that the neuropathic effects result from overexpression of NF-L mRNA, independent of NF-L protein effects (Cañete-Soler et al., 1999). The present study was undertaken to test for an RNA-mediated pathogenesis. Transgenic mice were derived using either an enhanced green fluorescent protein reporter construct or modified chimeric constructs that differ only in their 3′ untranslated regions (UTRs). Motor function and spinal cord histology were normal in mice expressing the unmodified reporter transgene. In mice expressing a chimeric transgene in which sequence of NF-L 3′ UTR was inserted into the 3′ UTR of the reporter transgene, we observed growth retardation and reduced kinetic activity during postnatal development. Older mice developed impairment of motor function and atrophy of nerve fibers in the ventral roots. A similar but more severe phenotype was observed when the chimeric transgene contained a 36 bp c-myc insert in an mRNA destabilizing element of the NF-L sequence. Our results suggest that neuropathic effects of overexpressing NF-L can occur at the level of transgene RNA and are mediated by sequences in the NF-L 3′ UTR.

Original languageEnglish (US)
Pages (from-to)7662-7670
Number of pages9
JournalJournal of Neuroscience
Volume22
Issue number17
StatePublished - Sep 1 2002
Externally publishedYes

Fingerprint

Intermediate Filaments
Motor Neurons
Transgenes
Transgenic Mice
3' Untranslated Regions
Light
Messenger RNA
Nerve Degeneration
Spinal Nerve Roots
Nerve Fibers
Atrophy
Spinal Cord
Histology
RNA
Phenotype
Growth

Keywords

  • EGFP reporter transgene
  • Motor neuron degeneration
  • Neurofilament-induced
  • Neuropathic RNA element
  • RNA-mediated
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nie, Z. J., Wu, J., Zhai, J., Lin, H., Ge, W., Schlaepfer, W. W., & Cañete-Soler, R. (2002). Untranslated element in neurofilament mRNA has neuropathic effect on motor neurons of transgenic mice. Journal of Neuroscience, 22(17), 7662-7670.

Untranslated element in neurofilament mRNA has neuropathic effect on motor neurons of transgenic mice. / Nie, Zhenying (Jane); Wu, Junhua; Zhai, Jinbin; Lin, Hong; Ge, Weiwen; Schlaepfer, William W.; Cañete-Soler, Rafaela.

In: Journal of Neuroscience, Vol. 22, No. 17, 01.09.2002, p. 7662-7670.

Research output: Contribution to journalArticle

Nie, ZJ, Wu, J, Zhai, J, Lin, H, Ge, W, Schlaepfer, WW & Cañete-Soler, R 2002, 'Untranslated element in neurofilament mRNA has neuropathic effect on motor neurons of transgenic mice', Journal of Neuroscience, vol. 22, no. 17, pp. 7662-7670.
Nie, Zhenying (Jane) ; Wu, Junhua ; Zhai, Jinbin ; Lin, Hong ; Ge, Weiwen ; Schlaepfer, William W. ; Cañete-Soler, Rafaela. / Untranslated element in neurofilament mRNA has neuropathic effect on motor neurons of transgenic mice. In: Journal of Neuroscience. 2002 ; Vol. 22, No. 17. pp. 7662-7670.
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