Abstract
Most human aneuploidies originate maternally, due in part to the presence of highly stringent checkpoints during male meiosis. Indeed, male sterility is common among aneuploid mice used to study chromosomal abnormalities, and male germline transmission of exogenous DNA has been rarely reported. Here we show that despite aberrant testis architecture, males of the aneuploid Tc1 mouse strain produce viable sperm and transmit human chromosome 21 to create aneuploid offspring. In these offspring, we mapped transcription, transcriptional initiation, enhancer activity, non-methylated DNA and transcription factor binding in adult tissues. Remarkably, when compared with mice derived from female passage of human chromosome 21, the chromatin condensation during spermatogenesis and the extensive epigenetic reprogramming specific to male germline transmission resulted in almost indistinguishable patterns of transcriptional deployment. Our results reveal an unexpected tolerance of aneuploidy during mammalian spermatogenesis, and the surprisingly robust ability of mouse developmental machinery to accurately deploy an exogenous chromosome, regardless of germline transmission.
Article and author information
Author details
Funding
Cancer Research UK (A20412)
- Christina Ernst
- Sarah J Aitken
- Nils Eling
- Frances Connor
- Tim F Rayner
- Margus Lukk
- Claudia Kutter
- Duncan T Odom
European Research Council (615584)
- Duncan T Odom
Wellcome (098024/Z/11/Z)
- Robert J Klose
Wellcome (106563/Z/14/A)
- Sarah J Aitken
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This investigation was approved by the Animal Welfare and Ethics Review Board and followed the Cambridge Institute guidelines for the use of animals in experimental studies under Home Office license PPL 70/7535.
Human subjects: Previously published human data from Ward et al. 2013 were used for comparisons in this study.
Reviewing Editor
- Edith Heard, Institut Curie, France
Publication history
- Received: August 1, 2016
- Accepted: November 14, 2016
- Accepted Manuscript published: November 18, 2016 (version 1)
- Accepted Manuscript updated: November 22, 2016 (version 2)
- Version of Record published: December 16, 2016 (version 3)
Copyright
© 2016, Ernst et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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