Maternal effects in infant and adult phenotypes of 5HT_1A and 5HT_1B receptor knockout mice

The influence of the pre- and postweaning maternal environment on the offspring's phenotype was examined in 5-HT1A and 5-HT1B receptor knockout mice (KO1A and KO1B, respectively). We have previously shown that, when born to and raised by homozygous dams of the same genotype, adult KO1A are more anxious than wild-type (WT) mice, and adult KO1B are hyperactive and slightly less anxious than WT mice. We extend our studies here to the behavioral results of the offspring's own genotype, when the dam's genotype is constant, and the effects of the dam's genotype when the offspring's genotype is constant. In Experiments 1 and 2, KO1A-/- pups produced less ultrasonic vocalizations (USV) than controls in an isolation test on postnatal Day 7 when born to and reared by KO1A dams, either -/- or +/-. Heterozygous F1 pups reared by KO1A-/- dams produced more USV and were less anxious in the plus-maze at 2 to 3 months of age than F1 pups born to and reared by WT dams (Experiment 3). F1 pups reared by KO1B-/- dams produced less USV and were more anxious in the plus-maze than F1 pups reared by WT dams (Experiment 4). The results support a role for maternal effects that may comprise direct effects such as the dam's behavior and nutritional care of the pup, and possibly more complex indirect effects through the establishment of idiosyncratic dam-pup dyadic interactions. We recommend that breeding techniques that rely on same genotype (mutant-mutant or WT-WT) breeding pairs not be used to generate offspring when the focus of research is the study of gene function, but rather when familial effects need to be studied.