Premium
Disruption of Normal Sleep Cycles in SULT4A1 Δ8/Δ8 Mutant Zebrafish
Author(s) -
Crittenden Frank,
Falany Charles
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.615.9
Subject(s) - zebrafish , frameshift mutation , biology , mutant , genetics , sleep (system call) , gene , mutation , exon , computer science , operating system
For 14 years, 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 sleep‐like behaviors during the day inconsistent with published reports on sleep in zebrafish. Zebrafish are largely diurnal organisms whose sleep is markedly inhibited by light. Thus, an increase in sleep‐like behavior during the day represents an abnormal behavior and warranted further systematic analysis. Using EthoVision video tracking software, this study demonstrates a significant increase in total sleep time and sleep bout frequency during the day in SULT4A1 Δ8/Δ8 fish. Night time sleep patterns remained unchanged. The identification of a physiological process (sleep), the normal function of which depends upon expression of SULT4A1, represents a major step forward in the search for this orphan SULT's function. (Supported by NIH grant R21MHO95946)