Motor neuron abnormalities correlate with impaired movement in zebrafish that express mutant superoxide dismutase 1

Katherine J. Robinson, Kristy C. Yuan, Emily K. Don, Alison L. Hogan, Claire G. Winnick, Madelaine C. Tym, Caitlin W. Lucas, Hamideh Shahheydari, Maxinne Watchon, Ian P. Blair, Julie D. Atkin, Garth A. Nicholson, Nicholas J. Cole, Angela S. Laird

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. ALS can be modeled in zebrafish (Danio rerio) through the expression of human ALS-causing genes, such as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein causes aberrant branching and shortening of spinal motor axons. Despite this, the functional relevance of this axon morphology remains elusive. Our aim was to determine whether this motor axonopathy is correlated with impaired movement in mutant (MT) SOD1-expressing zebrafish. Transgenic zebrafish embryos that express blue fluorescent protein (mTagBFP) in motor neurons were injected with either wild-type (WT) or MT (A4V) human SOD1 messenger ribonucleic acid (mRNA). At 48 hours post-fertilization, larvae movement (distance traveled during behavioral testing) was examined, followed by quantification of motor axon length. Larvae injected with MT SOD1 mRNA had significantly shorter and more aberrantly branched motor axons (p < 0.002) and traveled a significantly shorter distance during behavioral testing (p < 0.001) when compared with WT SOD1 and noninjected larvae. Furthermore, there was a positive correlation between distance traveled and motor axon length (R2 = 0.357, p < 0.001). These data represent the first correlative investigation of motor axonopathies and impaired movement in SOD1-expressing zebrafish, confirming functional relevance and validating movement as a disease phenotype for the testing of disease treatments for ALS.

LanguageEnglish
Pages8-14
Number of pages7
JournalZebrafish
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Feb 2019

Fingerprint

Motor Neurons
Zebrafish
motor neurons
Danio rerio
superoxide dismutase
axons
Axons
Amyotrophic Lateral Sclerosis
mutants
Larva
larvae
RNA
testing
neurodegenerative diseases
Superoxide Dismutase-1
Fertilization
shortenings
Neurodegenerative Diseases
branching
embryo (animal)

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • amyotrophic lateral sclerosis
  • behavioral testing
  • chemical screening
  • motor neuron disease
  • motor neurons

Cite this

@article{38a9c5cc8bfb4f96900a2228d0bf90de,
title = "Motor neuron abnormalities correlate with impaired movement in zebrafish that express mutant superoxide dismutase 1",
abstract = "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. ALS can be modeled in zebrafish (Danio rerio) through the expression of human ALS-causing genes, such as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein causes aberrant branching and shortening of spinal motor axons. Despite this, the functional relevance of this axon morphology remains elusive. Our aim was to determine whether this motor axonopathy is correlated with impaired movement in mutant (MT) SOD1-expressing zebrafish. Transgenic zebrafish embryos that express blue fluorescent protein (mTagBFP) in motor neurons were injected with either wild-type (WT) or MT (A4V) human SOD1 messenger ribonucleic acid (mRNA). At 48 hours post-fertilization, larvae movement (distance traveled during behavioral testing) was examined, followed by quantification of motor axon length. Larvae injected with MT SOD1 mRNA had significantly shorter and more aberrantly branched motor axons (p < 0.002) and traveled a significantly shorter distance during behavioral testing (p < 0.001) when compared with WT SOD1 and noninjected larvae. Furthermore, there was a positive correlation between distance traveled and motor axon length (R2 = 0.357, p < 0.001). These data represent the first correlative investigation of motor axonopathies and impaired movement in SOD1-expressing zebrafish, confirming functional relevance and validating movement as a disease phenotype for the testing of disease treatments for ALS.",
keywords = "amyotrophic lateral sclerosis, behavioral testing, chemical screening, motor neuron disease, motor neurons",
author = "Robinson, {Katherine J.} and Yuan, {Kristy C.} and Don, {Emily K.} and Hogan, {Alison L.} and Winnick, {Claire G.} and Tym, {Madelaine C.} and Lucas, {Caitlin W.} and Hamideh Shahheydari and Maxinne Watchon and Blair, {Ian P.} and Atkin, {Julie D.} and Nicholson, {Garth A.} and Cole, {Nicholas J.} and Laird, {Angela S.}",
note = "Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",
year = "2019",
month = "2",
day = "1",
doi = "10.1089/zeb.2018.1588",
language = "English",
volume = "16",
pages = "8--14",
journal = "Zebrafish",
issn = "1545-8547",
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Motor neuron abnormalities correlate with impaired movement in zebrafish that express mutant superoxide dismutase 1. / Robinson, Katherine J.; Yuan, Kristy C.; Don, Emily K.; Hogan, Alison L.; Winnick, Claire G.; Tym, Madelaine C.; Lucas, Caitlin W.; Shahheydari, Hamideh; Watchon, Maxinne; Blair, Ian P.; Atkin, Julie D.; Nicholson, Garth A.; Cole, Nicholas J.; Laird, Angela S.

In: Zebrafish, Vol. 16, No. 1, 01.02.2019, p. 8-14.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Motor neuron abnormalities correlate with impaired movement in zebrafish that express mutant superoxide dismutase 1

AU - Robinson, Katherine J.

AU - Yuan, Kristy C.

AU - Don, Emily K.

AU - Hogan, Alison L.

AU - Winnick, Claire G.

AU - Tym, Madelaine C.

AU - Lucas, Caitlin W.

AU - Shahheydari, Hamideh

AU - Watchon, Maxinne

AU - Blair, Ian P.

AU - Atkin, Julie D.

AU - Nicholson, Garth A.

AU - Cole, Nicholas J.

AU - Laird, Angela S.

N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. ALS can be modeled in zebrafish (Danio rerio) through the expression of human ALS-causing genes, such as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein causes aberrant branching and shortening of spinal motor axons. Despite this, the functional relevance of this axon morphology remains elusive. Our aim was to determine whether this motor axonopathy is correlated with impaired movement in mutant (MT) SOD1-expressing zebrafish. Transgenic zebrafish embryos that express blue fluorescent protein (mTagBFP) in motor neurons were injected with either wild-type (WT) or MT (A4V) human SOD1 messenger ribonucleic acid (mRNA). At 48 hours post-fertilization, larvae movement (distance traveled during behavioral testing) was examined, followed by quantification of motor axon length. Larvae injected with MT SOD1 mRNA had significantly shorter and more aberrantly branched motor axons (p < 0.002) and traveled a significantly shorter distance during behavioral testing (p < 0.001) when compared with WT SOD1 and noninjected larvae. Furthermore, there was a positive correlation between distance traveled and motor axon length (R2 = 0.357, p < 0.001). These data represent the first correlative investigation of motor axonopathies and impaired movement in SOD1-expressing zebrafish, confirming functional relevance and validating movement as a disease phenotype for the testing of disease treatments for ALS.

AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. ALS can be modeled in zebrafish (Danio rerio) through the expression of human ALS-causing genes, such as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein causes aberrant branching and shortening of spinal motor axons. Despite this, the functional relevance of this axon morphology remains elusive. Our aim was to determine whether this motor axonopathy is correlated with impaired movement in mutant (MT) SOD1-expressing zebrafish. Transgenic zebrafish embryos that express blue fluorescent protein (mTagBFP) in motor neurons were injected with either wild-type (WT) or MT (A4V) human SOD1 messenger ribonucleic acid (mRNA). At 48 hours post-fertilization, larvae movement (distance traveled during behavioral testing) was examined, followed by quantification of motor axon length. Larvae injected with MT SOD1 mRNA had significantly shorter and more aberrantly branched motor axons (p < 0.002) and traveled a significantly shorter distance during behavioral testing (p < 0.001) when compared with WT SOD1 and noninjected larvae. Furthermore, there was a positive correlation between distance traveled and motor axon length (R2 = 0.357, p < 0.001). These data represent the first correlative investigation of motor axonopathies and impaired movement in SOD1-expressing zebrafish, confirming functional relevance and validating movement as a disease phenotype for the testing of disease treatments for ALS.

KW - amyotrophic lateral sclerosis

KW - behavioral testing

KW - chemical screening

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U2 - 10.1089/zeb.2018.1588

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