A novel system to accelerate the progression of nerve degeneration in transgenic mouse models of neuropathies

Osefame Ewaleifoh, Minh Trinh, John W. Griffin, Thien Nguyen

Research output: Contribution to journalArticle

Abstract

Axon degeneration is a common hallmark of many neurodegenerative diseases. There is now an abundance of spontaneous and genetically engineered mice available to study the mechanisms of axonal degeneration and to screen for axonal protective agents. However, many of these mouse models exhibit slow progressive axonal loss which can span over many months. Consequently, there is a pressing need to accelerate the pace of axonal loss over a short interval for high-throughput screening of pharmacological and genetic therapies. Here, we present a novel technique using acrylamide, an axonal neurotoxin, to provoke rapid axonal degeneration in murine models of neuropathies. The progressive axonal loss which typically occurs over 8. months was reproduced within 7 to 10. days of the acrylamide intoxication. This approach was successfully applied to Myelin Associated Glycoprotein knockout (MAG-/-) mouse and Trembler-J mouse, a popular murine model of Charcot-Marie-Tooth disease type 1 (CMT-1). Acrylamide intoxication in transgenic mouse models offers a novel experimental approach to accelerate the rate of axonal loss over short intervals for timely in vivo studies of nerve degeneration. This report also provides for the first time an animal model for medication or toxin-induced exacerbation of pre-existing neuropathies, a phenomenon widely reported in patients with neuropathies.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalExperimental Neurology
Volume237
Issue number1
DOIs
StatePublished - Sep 2012

Fingerprint

Nerve Degeneration
Acrylamide
Transgenic Mice
Myelin-Associated Glycoprotein
Charcot-Marie-Tooth Disease
Protective Agents
Neurotoxins
Knockout Mice
Neurodegenerative Diseases
Genetic Therapy
Axons
Animal Models
Pharmacology

Keywords

  • Acrylamide
  • Animal model
  • Axonal degeneration
  • Charcot-Marie-Tooth

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

A novel system to accelerate the progression of nerve degeneration in transgenic mouse models of neuropathies. / Ewaleifoh, Osefame; Trinh, Minh; Griffin, John W.; Nguyen, Thien.

In: Experimental Neurology, Vol. 237, No. 1, 09.2012, p. 153-159.

Research output: Contribution to journalArticle

Ewaleifoh, Osefame ; Trinh, Minh ; Griffin, John W. ; Nguyen, Thien. / A novel system to accelerate the progression of nerve degeneration in transgenic mouse models of neuropathies. In: Experimental Neurology. 2012 ; Vol. 237, No. 1. pp. 153-159.
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