Research article

Chromosome Y variants from different inbred mouse strains are linked to differences in the morphologic and molecular responses of cardiac cells to postpubertal testosterone

Bastien Llamas^1,3†, Ricardo A Verdugo^2†, Gary A Churchill² and Christian F Deschepper^1*

• * Corresponding author: Christian F Deschepper deschec@ircm.qc.ca

• † Equal contributors

Author Affiliations

¹ Experimental Cardiovascular Biology Research Unit, Institut de recherches cliniques de Montréal (IRCM) and Université de Montréal, 110 Pine Ave West, Montréal (QC), H2W 1R7, Canada

² The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA

³ Present address: Australian Centre for Ancient DNA, University of Adelaide, SA 5005, Australia

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BMC Genomics 2009, 10:150 doi:10.1186/1471-2164-10-150

Published: 7 April 2009

Abstract

Background

We have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (ChrY^C57) was substituted for that of A/J mice (ChrY^A), cardiomyocytes from the resulting "chromosome substitution" C57BL/6J-chrY^A strain were smaller than that of their C57BL/6J counterparts. In reverse, when chrY^A from A/J mice was substituted for that of chrY^C57, cardiomyocytes from the resulting A/J-chrY^C57 strain were larger than in their A/J counterparts. We further used these strains to test whether: 1) the origin of chrY could also be linked to differences in the profile of gene expression in the hearts of adult male mice, and 2) post-pubertal testosterone could play a role in the differential morphologic and/or molecular effects of chrY^C57 and chrY^A.

Results

The increased size of cardiomyocytes from adult male C57BL/6J mice compared to C57BL/6J-chrY^A resulted from the absence of hypertrophic effects of post-pubertal testosterone on cells from the latter strain. However, gene profiling revealed that the latter effect could not be explained on the basis of an insensitivity of cells from C57BL/6J-chrY^A to androgens, since even more cardiac genes were affected by post-pubertal testosterone in C57BL/6J-chrY^A hearts than in C57BL/6J. By testing for interaction between the effects of surgery and strain, we identified 249 "interaction genes" whose expression was affected by post-pubertal testosterone differentially according to the genetic origin of chrY. These interaction genes were found to be enriched within a limited number of signaling pathways, including: 1) p53 signaling, which comprises the interacting genes Ccnd1, Pten and Cdkn1a that are also potential co-regulators of the androgen receptors, and 2) circadian rhythm, which comprises Arntl/Bmal1, which may in turn regulate cell growth via the control of Cdkn1a.

Conclusion

Although post-pubertal testosterone increased the size of cardiomyocytes from male C56BL/6J mice but not that from their C57BL/6J-chrY^A counterparts, it affected gene expression in the hearts from both strains. However, several cardiac genes responded to post-pubertal testosterone in a strict strain-selective manner, which provides possible mechanisms explaining how chrY may, in part via interference with androgen regulatory events, be linked to morphologic differences of cardiac cells of adult male mice.