Maternal care of heterozygous dopamine receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions.,Genes, Brain and Behavior

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Maternal care of heterozygous dopamine receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions.
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2020-04-18 , DOI: 10.1111/gbb.12655
Jelle Knop _{1,

2} , Marinus H van IJzendoorn _{3,

4} , Marian J Bakermans-Kranenburg ₅ , Marian Joëls _{1,

6} , Rixt van der Veen _{1,

2}

Affiliation

The differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (DRD4) 7‐repeat as a main factor in exhibiting these for better and for worse characteristics. However, human studies lack the genetic and environmental control offered by animal experiments, complicating assessment of causal relations. To study differential susceptibility in an animal model, we exposed Drd4^+/− mice and control litter mates to a limited nesting/bedding (LN), standard nesting (SN) or communal nesting (CN) rearing environment from postnatal day (P) 2‐14. Puberty onset was examined from P24 to P36 and adult females were assessed on maternal care towards their own offspring. In both males and females, LN reared mice showed a delay in puberty onset that was partly mediated by a reduction in body weight at weaning, irrespective of Drd4 genotype. During adulthood, LN reared females exhibited characteristics of poor maternal care, whereas dams reared in CN environments showed lower rates of unpredictability towards their own offspring. Differential susceptibility was observed only for licking/grooming levels of female offspring towards their litter; LN reared Drd4^+/− mice exhibited the lowest and CN reared Drd4^+/− mice the highest levels of licking/grooming. These results indicate that both genetic and early‐environmental factors play an important role in shaping maternal care of the offspring for better and for worse.

中文翻译：

杂合多巴胺受体D4基因敲除小鼠的产妇护理：对早期养育条件的敏感性不同。

差异敏感性假设提出，更容易受到不利饲养条件的负面影响的个体也可能会从丰富的环境中受益更多。来自人类实验的证据表明，多巴胺受体D4（DRD4）7重复的功效较低，是表现出这些特征好坏的主要因素。然而，人类研究缺乏动物实验提供的遗传和环境控制，这使得因果关系的评估变得复杂。为了研究动物模型中的敏感性差异，我们暴露了Drd4 ^+/-从出生后（P）2-14开始，将小鼠和对照组的幼仔交配到有限的筑巢/铺垫（LN），标准筑巢（SN）或公共筑巢（CN）的饲养环境。从P24至P36检查青春期发作，并评估成年雌性对其后代的孕产妇保健。在LN饲养的雄性和雌性小鼠中，不论Drd4基因型如何，其青春期发作延迟都部分由断奶时体重减轻所介导。在成年期，以LN饲养的雌性动物表现出较差的孕产妇护理特征，而在CN环境中饲养的水坝显示出对其后代的不可预测性较低。仅在雌性后代朝着其产仔的舔//修饰水平上观察到差异敏感性。LN饲养Drd4 ^+/-小鼠表现出最低的舔食/修饰水平，而CN饲养的Drd4 ^+/-小鼠表现出最高的舔/修饰水平。这些结果表明，遗传因素和早期环境因素在影响后代孕产妇保健方面起着重要作用。

更新日期：2020-04-18

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