title: Tissue-specific expression and in vivo regulation of zebrafish orthologues of mammalian genes related to symptomatic hypomagnesemia.
abstract: Introduction of zebrafish as a model for human diseases with symptomatic hypomagnesemia urges to identify the regulatory transport genes involved in zebrafish Mg(2+) physiology. In humans, mutations related to hypomagnesemia are located in the genes TRPM6 and CNNM2, encoding for a Mg(2+) channel and transporter, respectively; EGF (epidermal growth factor); SLC12A3, which encodes for the Na(+)-Cl(-) co-transporter NCC; KCNA1 and KCNJ10, encoding for the K(+) channels Kv1.1 and Kir4.1, respectively; and FXYD2, which encodes for the γ-subunit of the Na(+),K(+)-ATPase. Orthologues of these genes were found in the zebrafish genome. For cnnm2, kcna1 and kcnj10, two conserved paralogues were retrieved. Except for fxyd2, kcna1b and kcnj10 duplicates, transcripts of orthologues were detected in ionoregulatory organs such as the gills, kidney and gut. Gene expression analyses in zebrafish acclimated to a Mg(2+)-deficient (0 mM Mg(2+)) or a Mg(2+)-enriched (2 mM Mg(2+)) water showed that branchial trpm6, gut cnnm2b and renal slc12a3 responded to ambient Mg(2+). When changing the Mg(2+) composition of the diet (the main source for Mg(2+) in fish) to a Mg(2+)-deficient (0.01 % (w/w) Mg) or a Mg(2+)-enriched diet (0.7 % (w/w) Mg), mRNA expression of branchial trpm6, gut trpm6 and cnnm2 duplicates, and renal trpm6, egf, cnnm2a and slc12a3 was the highest in fish fed the Mg(2+)-deficient diet. The gene regulation patterns were in line with compensatory mechanisms to cope with Mg(2+)-deficiency or surplus. Our findings suggest that trpm6, egf, cnnm2 paralogues and slc12a3 are involved in the in vivo regulation of Mg(2+) transport in ionoregulatory organs of the zebrafish model.
authors: Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Francisco J
authors: FJ
authors: Arjona
authors: Yu-Xuan
authors: YX
authors: Chen
authors: Gert
authors: G
authors: Flik
authors: René J
authors: RJ
authors: Bindels
authors: Joost G
authors: JG
authors: Hoenderop
mesh_terms: D000818:Animals; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005880:Gills / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008275:Magnesium Deficiency / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016213:Cyclins; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D064486:Solute Carrier Family 12, Member 3; D050053:TRPM Cation Channels; D029961:Zebrafish Proteins; D051662:Kv1.1 Potassium Channel; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium
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