Lithium treatment of NZB/W F1 and parental mice leads to alterations in kidney mRNA levels: further evidence for genetic and gender influences on Li responsiveness

Recent studies have indicated that both gender and genetic factors play a r ole in the physiologic response of mice to acute and chronic administration of lithium. In both cases, the studies involved the kidney. Therefore, the present study was initiated to better understand the molecular mechanisms in the kidney that may be responsible for these differences in response to Li. Male and female NZB/W mice, as well as females of the parental strains (NZB and NZW), were subjected to an acute course of intraperitoneal Li admi nistration and then the kidneys removed, total RNA isolated and mRNA levels for a subset of molecules known to be expressed on renal tubule cells, kno wn to be regulated by androgens, or known to be potent regulators of transc riptional activity, were assessed by semiquantitative RT-PCR. Li treatment was demonstrated to significantly influence mRNA levels for a number of the se molecules in a gender- and/or strain-specific manner. For a subset of th e molecules assessed, Li treatment led to significant alterations in mRNA l evels independent of gender and strain, indicating specificity to the obser ved gender and strain influences. These results support the conclusion that Li responsiveness in mice can be strongly influenced by both gender and ge netic factors. However, it was not possible to directly correlate the obser ved changes in mRNA levels for specific molecules with the previously defin ed variations in physiologic responses to Li in vivo. Therefore, additional studies will be required to better define the molecular mechanisms of Li a ction. Copyright (C) 2000 by Marcel Dekker, Inc.