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Research ArticleArticle

Activity Suppression Behavior Phenotype in SULT4A1 Frameshift Mutant Zebrafish

Frank Crittenden, Holly R. Thomas, John M. Parant and Charles N. Falany
Drug Metabolism and Disposition July 2015, 43 (7) 1037-1044; DOI: https://doi.org/10.1124/dmd.115.064485
Frank Crittenden
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama (F.C., H.R.T., J.M.P., C.N.F.)
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Holly R. Thomas
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama (F.C., H.R.T., J.M.P., C.N.F.)
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John M. Parant
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama (F.C., H.R.T., J.M.P., C.N.F.)
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Charles N. Falany
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama (F.C., H.R.T., J.M.P., C.N.F.)
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This article has a correction. Please see:

  • Correction to: “Activity Suppression Behavior Phenotype in SULT4A1 Frameshift Mutant Zebrafish” - August 01, 2015

Abstract

Since its identification in 2000, sulfotransferase (SULT) 4A1 has presented an enigma to the field of cytosolic SULT biology. SULT4A1 is exclusively expressed in neural tissue, is highly conserved, and has been identified in every vertebrate studied to date. Despite this singular level of conservation, no substrate or function for SULT4A1 has been identified. Previous studies demonstrated that SULT4A1 does not bind the obligate sulfate donor, 3′-phosphoadenosine-5′-phosphosulfate, yet SULT4A1 is classified as a SULT superfamily member based on sequence and structural similarities to the other SULTs. In this study, transcription activator-like effector nucleases were used to generate heritable mutations in the SULT4A1 gene of zebrafish. The mutation (SULT4A1Δ8) consists of an 8-nucleotide deletion within the second exon of the gene, resulting in a frameshift mutation and premature stop codon after 132 AA. During early adulthood, casual observations were made that mutant zebrafish were exhibiting excessively sedentary behavior during the day. These observations were inconsistent with published reports on activity in zebrafish that are largely diurnal organisms and are highly active during the day. Thus, a decrease in activity during the day represents an abnormal behavior and warranted further systematic analysis. EthoVision video tracking software was used to monitor activity levels in wild-type (WT) and SULT4A1Δ8/Δ8 fish over 48 hours of a normal light/dark cycle. SULT4A1Δ8/Δ8 fish were shown to exhibit increased inactivity bout length and frequency as well as a general decrease in daytime activity levels when compared with their WT counterparts.

Footnotes

    • Received March 27, 2015.
    • Accepted April 30, 2015.
  • This work was supported by the National Institutes of Health [Grants R21MH095946 and P30NS47466].

  • dx.doi.org/10.1124/dmd.115.064485.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 43 (7)
Drug Metabolism and Disposition
Vol. 43, Issue 7
1 Jul 2015
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Research ArticleArticle

Activity in SULT4A1 Ko Zebrafish

Frank Crittenden, Holly R. Thomas, John M. Parant and Charles N. Falany
Drug Metabolism and Disposition July 1, 2015, 43 (7) 1037-1044; DOI: https://doi.org/10.1124/dmd.115.064485

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Research ArticleArticle

Activity in SULT4A1 Ko Zebrafish

Frank Crittenden, Holly R. Thomas, John M. Parant and Charles N. Falany
Drug Metabolism and Disposition July 1, 2015, 43 (7) 1037-1044; DOI: https://doi.org/10.1124/dmd.115.064485
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