Maternal care of heterozygous dopamine receptorD4knockout mice: Differential susceptibility to early-life rearing conditions

Jelle Knop, Marinus H. van IJzendoorn, Marian J. Bakermans-Kranenburg, Marian Joels, Rixt van der Veen*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    7 Citations (Scopus)
    109 Downloads (Pure)


    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 exposedDrd4(+/-)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 ofDrd4genotype. 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 rearedDrd4(+/-)mice exhibited the lowest and CN rearedDrd4(+/-)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.

    Original languageEnglish
    Article numbere12655
    Number of pages12
    JournalGenes, Brain and Behavior
    Issue number7
    Early online date15-Jun-2020
    Publication statusPublished - Sept-2020


    • animal model
    • communal nesting
    • differential susceptibility
    • dopamine receptor D4
    • early-life adversity
    • gene-environment interaction
    • intergenerational transmission
    • limited bedding
    • nesting
    • maternal care
    • puberty onset
    • ONSET

    Cite this