Generation and characterization of mice lacking the zinc uptake transporter ZIP3.
The mouse ZIP3 (SLC39A3) gene encodes an eight-transmembrane-domain protein that has been conserved in mammals and can function to transport zinc. To analyze the expression of ZIP3 in the early embryo and neonate and to determine its in vivo function, we generated ZIP3 null mice in which the ZIP3 open reading frame was replaced with that of the enhanced green fluorescent protein (EGFP) reporter. EGFP fluorescence revealed that ZIP3 was expressed in the inner cell mass of the blastocyst and later during embryonic development in many tissues. Elevated expression was apparent in the embryonic brain and neurotube and neonatal gonads. Homozygous knockout mice were viable and fertile and under normal growth conditions exhibited no obvious phenotypic abnormalities. Deletion of ZIP3 did not alter zinc homeostasis at the molecular level as assessed by essential metal levels and the expression of zinc-responsive genes. In knockout mice stressed with a zinc-deficient diet during pregnancy or at weaning, a subtle increase in the sensitivity to abnormal morphogenesis of the embryo and to depletion of thymic pre-T cells, respectively, was noted. These results suggest that this protein plays an ancillary role in zinc homeostasis in mice.
Dufner-Beattie
Jodi
J
Department of Biochemistry and Molecular Biology, Mail Stop 3030, University of Kansas Medical Center, 39th and Rainbow Blvd., Kansas City, Kansas 66160-7421, USA.
Huang
Zhixin L
ZL
Geiser
Jim
J
Xu
Wenhao
W
Andrews
Glen K
GK
D000818:Animals; D000831:Animals, Newborn; D001755:Blastocyst / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D018274:Electroporation; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology; D014018:Tissue Distribution; D015032:Zinc / Q000032:analysis / Q000172:deficiency / Q000378:metabolism*
D002352:Carrier Proteins; D027682:Cation Transport Proteins; C498426:Slc39a3 protein, mouse; C017800:zinc-binding protein; D049452:Green Fluorescent Proteins; D015032:Zinc