Previously this laboratory has identified the mouse Slc39a8 gene encoding the ZIPS transporter, important in cadmium uptake. ZIPS functions endogenously as a electroneutral Zn2+/(HCO3-)(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 S1c39a8(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. S1c39a8(neo) is a hypomorphic allele, because S1c39a8(neo/neo) homozygotes exhibit dramatically decreased ZIP8 expression in embryo, fetus, and visceral yolk sac - in comparison to their littermate wild-type controls. This ZIPS hypomorph will be instrumental in studying developmental and in utero physiological functions of the ZIP8 transporter. (C) 2011 Elsevier Inc. All rights reserved.