Weller Aron, Leguisamo Ana Christina, Towns Lorraine, Ramboz Silvie, Bagiella Emilia, Hofer Myron, Hen Rene, Brunner Dani
Department of Psychiatry and Sackler, Institute of Developmental Psychobiology, Columbia University, New York, NY 10032, USA.
Dev Psychobiol. 2003 Mar;42(2):194-205. doi: 10.1002/dev.10079.
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.
在5-羟色胺1A和5-羟色胺1B受体基因敲除小鼠（分别为KO1A和KO1B）中，研究了断奶前后母体环境对后代表型的影响。我们之前已经表明，当由相同基因型的纯合母鼠生育并抚养长大时，成年KO1A小鼠比野生型（WT）小鼠更焦虑，而成年KO1B小鼠则多动，且焦虑程度略低于WT小鼠。我们在此将研究扩展到母鼠基因型不变时后代自身基因型的行为结果，以及后代基因型不变时母鼠基因型的影响。在实验1和实验2中，当由KO1A母鼠（-/-或+/-）生育并抚养时，KO1A-/-幼崽在出生后第7天的隔离试验中发出的超声波叫声（USV）比对照组少。由KO1A-/-母鼠抚养的杂合F1幼崽在2至3个月大时发出的USV更多，并且在加迷宫实验中比由WT母鼠生育并抚养的F1幼崽更不焦虑（实验3）。由KO1B-/-母鼠抚养的F1幼崽发出的USV更少，并且在加迷宫实验中比由WT母鼠抚养的F1幼崽更焦虑（实验4）。这些结果支持母体效应的作用，母体效应可能包括直接效应，如母鼠对幼崽的行为和营养照顾，以及可能通过建立独特的母鼠-幼崽二元互动产生的更复杂的间接效应。我们建议，当研究重点是基因功能时，不要使用依赖相同基因型（突变体-突变体或WT-WT）繁殖对来产生后代，而当需要研究家族效应时则可以使用。
