Show simple item record Cook, Matthew en_US Munger, Steven C. en_US Capel, Blanche en_US 2011-06-21T17:27:32Z 2011-06-21T17:27:32Z 2011 en_US
dc.identifier.citation Cook,Matthew S.;Munger,Steven C.;Nadeau,Joseph H.;Capel,Blanche. 2011. Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background. Development 138(1): 23-32. en_US
dc.identifier.issn 0950-1991 en_US
dc.description.abstract Human germ cell tumors show a strong sensitivity to genetic background similar to Dnd1(Ter/Ter) mutant mice, where testicular teratomas arise only on the 129/SvJ genetic background. The introduction of the Bax mutation onto mixed background Dnd1(Ter/Ter) mutants, where teratomas do not typically develop, resulted in a high incidence of teratomas. However, when Dnd1(Ter/Ter); Bax(-/-) double mutants were backcrossed to C57BL/6J, no tumors arose. Dnd1(Ter/Ter) germ cells show a strong downregulation of male differentiation genes including Nanos2. In susceptible strains, where teratomas initiate around E15.5-E17.5, many mutant germ cells fail to enter mitotic arrest in G0 and do not downregulate the pluripotency markers NANOG, SOX2 and OCT4. We show that DND1 directly binds a group of transcripts that encode negative regulators of the cell cycle, including p27(Kip1) and p21(Cip1). P27(Kip1) and P21(Cip1) protein are both significantly decreased in Dnd1(Ter/Ter) germ cells on all strain backgrounds tested, strongly suggesting that DND1 regulates mitotic arrest in male germ cells through translational regulation of cell cycle genes. Nonetheless, in C57BL/6J mutants, germ cells arrest prior to M-phase of the cell cycle and downregulate NANOG, SOX2 and OCT4. Consistent with their ability to rescue cell cycle arrest, C57BL/6J germ cells overexpress negative regulators of the cell cycle relative to 129/SvJ. This work suggests that reprogramming of pluripotency in germ cells and prevention of tumor formation requires cell cycle arrest, and that differences in the balance of cell cycle regulators between 129/SvJ and C57BL/6 might underlie differences in tumor susceptibility. en_US
dc.language.iso en_US en_US
dc.relation.isversionof doi:10.1242/dev.057000 en_US
dc.subject germ cell en_US
dc.subject cell cycle en_US
dc.subject testicular teratoma en_US
dc.subject mouse en_US
dc.subject congenital testicular teratomas en_US
dc.subject embryonic stem-cells en_US
dc.subject ter mutation en_US
dc.subject dead-end en_US
dc.subject suppresses meiosis en_US
dc.subject 129/sv-ter mice en_US
dc.subject messenger-rna en_US
dc.subject united-states en_US
dc.subject expression en_US
dc.subject developmental biology en_US
dc.title Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US 2011-1-1 en_US
duke.description.endpage 32 en_US
duke.description.issue 1 en_US
duke.description.startpage 23 en_US
duke.description.volume 138 en_US
dc.relation.journal Development en_US

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