BMC Genomics 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 BioMed Central Open Access Address: 1Experimental Cardiovascular Biology Research Unit, Institut de recherches cliniques de Montréal (IRCM) and Université de Montréal, 110 Pine Ave West, Montréal (QC), H2W 1R7, Canada, 2The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA and 3Present address: Australian Centre for Ancient DNA, University of Adelaide, SA 5005, Australia Email: Bastien Llamas - bastien.llamas@adelaide.edu.au; Ricardo A Verdugo - ricardo.verdugo@jax.org; Gary A Churchill - gary.churchill@jax.org; Christian F Deschepper* - deschec@ircm.qc.ca * Corresponding author †Equal contributors Published: 7 April 2009 BMC Genomics 2009, 10:150 doi:10.1186/1471-2164-10-150 This article is available from: http://www.biomedcentral.com/1471-2164/10/150 Received: 6 October 2008 Accepted: 7 April 2009 © 2009 Llamas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: We have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (ChrYC57) was substituted for that of A/J mice (ChrYA), cardiomyocytes from the resulting "chromosome substitution" C57BL/6J-chrYA strain were smaller than that of their C57BL/6J counterparts. In reverse, when chrYA from A/J mice was substituted for that of chrYC57, cardiomyocytes from the resulting A/J-chrYC57 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 chrYC57 and chrYA. Results: The increased size of cardiomyocytes from adult male C57BL/6J mice compared to C57BL/6J- chrYA 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-chrYA to androgens, since even more cardiac genes were affected by post-pubertal testosterone in C57BL/6J-chrYA 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-chrYA 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. Page 1 of 11 (page number not for citation purposes)