title: Generation of a Slc39a8 hypomorph mouse: markedly decreased ZIP8 Zn²⁺/(HCO₃⁻)₂ transporter expression.
abstract: Previously this laboratory has identified the mouse Slc39a8 gene encoding the ZIP8 transporter, important in cadmium uptake. ZIP8 functions endogenously as a electroneutral Zn(2+)/(HCO(3)(-))(2) symporter, moving both ions into the cell. The overall physiological importance of ZIP8 remains unclear. Herein we describe generation of a mouse line carrying the Slc39a8(neo) allele, containing the Frt-flanked neomycin-resistance (neo) mini-cassette in intron 3 and loxP sites in introns 3 and 6. Cre recombinase functions correctly in Escherichia coli and in adeno-Cre-infected mouse fetal fibroblasts, but does not function in the intact mouse for reasons not clear. Slc39a8(neo) is a hypomorphic allele, because Slc39a8(neo/neo) homozygotes exhibit dramatically decreased ZIP8 expression in embryo, fetus, and visceral yolk sac - in comparison to their littermate wild-type controls. This ZIP8 hypomorph will be instrumental in studying developmental and in utero physiological functions of the ZIP8 transporter.
authors.affiliation: Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.forename: Hongbin
authors.initials: H
authors.lastname: Dong
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Dalton
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Nebert
mesh_terms: D000818:Animals; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000172:deficiency* / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D007438:Introns; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009355:Neomycin / Q000494:pharmacology; D010920:Placenta; D011247:Pregnancy; D015017:Yolk Sac / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; C499256:Slc39a8 protein, mouse; D009355:Neomycin