X-linked and lineage-dependent inheritance of coping responses to stress (original) (raw)

Abstract

Coping—or how one routinely deals with stress—is a complex behavioral trait with bearing on chronic disease and susceptibility to psychiatric disorders. This complexity is a result of not only underlying multigenic factors, but also important non-genetic ones. The defensive burying (DB) test, although originally developed as a test of anxiety, can accurately measure differences in coping strategies by assaying an animal’s behavioral response to an immediate threat with ethological validity. Using offspring derived from reciprocal crosses of two inbred rat strains differing in DB behaviors, we provide convergent phenotypic and genotypic evidence that coping styles are inherited in an X-linked fashion. We find that first-generation (F1) males, but not females, show maternally derived coping styles, and second-generation (F2) females, but not males, show significant differences in coping styles when separated by grandmaternal lineage. By using a linear modeling approach to account for covariate effects (sex and lineage) in QTL analysis, we map three quantitative trait loci (QTL) on the X Chromosome (Chr) (Coping-1, Approach-1, and Approach-2) associated with coping behaviors in the DB paradigm. Distinct loci were associated with different aspects of coping, and their effects were modulated by both the sex and lineage of the animals, demonstrating the power of the general linear modeling approach and the important interplay of allelic and non-allelic factors in the inheritance of coping behaviors.

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Acknowledgements

We thank Amber E. Baum for assistance with DNA isolation, and Hoda Mahmoudi for assistance with initial phenotype characterization and DNA isolation. Photographs used in Fig. 1 were kindly provided by William P. Pare. This study was supported by NIH grant MH60789. J.S. Takahashi is an Investigator in the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Ward 9-190 Chicago, Illinois 60611, USA
    Nasim Ahmadiyeh, Leah C. Solberg & Eva E. Redei
  2. Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208, USA
    Nasim Ahmadiyeh, Kazuhiro Shimomura & Joseph S. Takahashi
  3. Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
    Nasim Ahmadiyeh, Kazuhiro Shimomura, Leah C. Solberg & Joseph S. Takahashi
  4. The Jackson Laboratory, Bar Harbor, Maine 04609, USA
    Gary A. Churchill

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  1. Nasim Ahmadiyeh
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  2. Gary A. Churchill
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  3. Kazuhiro Shimomura
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  4. Leah C. Solberg
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  5. Joseph S. Takahashi
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  6. Eva E. Redei
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Correspondence toNasim Ahmadiyeh.

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Ahmadiyeh, N., Churchill, G.A., Shimomura, K. _et al._X-linked and lineage-dependent inheritance of coping responses to stress .Mamm Genome 14, 748–757 (2003). https://doi.org/10.1007/s00335-003-2292-x

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