Activity Suppression Behavior Phenotype in SULT4A1 Frameshift Mutant Zebrafish

Crittenden, F., Thomas, H.R., Parant, J.M., Falany, C.N.
Drug metabolism and disposition: the biological fate of chemicals   43(7): 1037-44 (Journal)
Registered Authors
Falany, Charles, Parant, John
animal models, sulfate conjugation/sulfotransferases/SULT
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Anxiety/genetics
  • Anxiety/psychology
  • Base Sequence
  • Deoxyribonucleases/administration & dosage
  • Deoxyribonucleases/pharmacology
  • Embryo, Nonmammalian
  • Exons
  • Frameshift Mutation/genetics*
  • Microinjections
  • Molecular Sequence Data
  • Motor Activity/genetics*
  • Mutation
  • Social Behavior
  • Sulfotransferases/genetics*
  • Sulfotransferases/metabolism*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
25934576 Full text @ Drug Metab. Dispos.
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 (PAPS), 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 (TALENs) were used to generate heritable mutations in the SULT4A1 gene of zebrafish. The mutation (SULT4A1(Δ8)) consists of an 8 nucleotide deletion within the second exon of the gene, resulting in a frameshift mutation and premature stop codon after 182 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 which 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 SULT4A1(Δ8/Δ8) fish over 48 hours of a normal light/dark cycle. SULT4A1(Δ8/Δ8) fish were shown to exhibit increased inactivity bout length and frequency as well as a general decrease in daytime activity levels when compared to their WT counterparts.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes
This article is corrected by ZDB-PUB-220906-25.