title: Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis.
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.
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Christina
authors.identifier: 0000-0002-3569-2209
authors.initials: C
authors.lastname: Ernst
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pike
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Histopathology, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Aitken
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.|Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United states.|Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Long
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nils
authors.initials: N
authors.lastname: Eling
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Lovorka
authors.initials: L
authors.lastname: Stojic
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Ward
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Frances
authors.initials: F
authors.lastname: Connor
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Rayner
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Margus
authors.initials: M
authors.lastname: Lukk
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Robert J
authors.identifier: 0000-0002-8726-7888
authors.initials: RJ
authors.lastname: Klose
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden.
authors.forename: Claudia
authors.identifier: 0000-0002-8047-0058
authors.initials: C
authors.lastname: Kutter
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Duncan T
authors.identifier: 0000-0001-6201-5599
authors.initials: DT
authors.lastname: Odom
mesh_terms: D000818:Animals; D002877:Chromosomes, Human / Q000378:metabolism*; D020732:Cytogenetic Analysis; D005854:Germ Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D014158:Transcription, Genetic
keywords: aneuploidy; chromosomes; epigenetic reprogramming; genes; human; male germline; meiosis; mouse