Alterations of postnatal immune development in the mouse by marginal gestational zinc deficiency

An improved model for studying the immunodeficiencies associated with normal-term low-birth-weight infants has been generated in the mouse by a marginal deficiency of zinc during gestation. A/J mice received diet containing 3.5 μg Zn/g diet (MZD) or 30 μg Zn/g diet ad libitum (ZA) or in restricted amounts (RES) from day 0 to day 17 of gestation. MZD litter sizes were 68% of ZA litters, yet these offspring had normal survival rates. MZD dams and fetuses had transient reductions of zinc which returned to normal by birth since zinc replenishment began on day 17 of gestation. MZD fetuses had normal body lengths but significantly lower birth weights (74% of ZA), indicating an asymmetric form of intrauterine growth retardation. At day 13 and at puberty, MZD offspring exhibited a 40% reduction in response to a T-independent antigen. Therefore, a marginal deficiency of zinc in utero resulted in low-birth-weight offspring with immunodeficiencies not readily repairable by zinc repletion.