Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1

Development
Liang ZhaoPeter Koopman

Abstract

Genes related to Dmrt1, which encodes a DNA-binding DM domain transcription factor, act as triggers for primary sex determination in a broad range of metazoan species. However, this role is fulfilled in mammals by Sry, a newly evolved gene on the Y chromosome, such that Dmrt1 has become dispensable for primary sex determination and instead maintains Sertoli cell phenotype in postnatal testes. Here, we report that enforced expression of Dmrt1 in XX mouse fetal gonads using a Wt1-BAC transgene system is sufficient to drive testicular differentiation and male secondary sex development. XX transgenic fetal gonads showed typical testicular size and vasculature. Key ovarian markers, including Wnt4 and Foxl2, were repressed. Sertoli cells expressing the hallmark testis-determining gene Sox9 were formed, although they did not assemble into normal testis cords. Other bipotential lineages differentiated into testicular cell types, including steroidogenic fetal Leydig cells and non-meiotic germ cells. As a consequence, male internal and external reproductive organs developed postnatally, with an absence of female reproductive tissues. These results reveal that Dmrt1 has retained its ability to act as the primary testis-determining trigger...Continue Reading

References

May 9, 1991·Nature·P KoopmanR Lovell-Badge
Mar 7, 1998·Nature·C S RaymondD Zarkower
Jun 30, 2001·Nature Genetics·V P VidalA Schedl
Aug 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Indrajit NandaManfred Schartl
Nov 20, 2002·Cytogenetic and Genome Research·J A Marshall Graves
Mar 26, 2003·Genes & Development·Jennifer BrennanBlanche Capel
Aug 20, 2004·Nature·Déborah Bourc'his, Timothy H Bestor
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jana KoubovaDavid C Page
Apr 1, 2006·Science·Josephine BowlesPeter Koopman
Aug 31, 2007·Human Molecular Genetics·Chris OttolenghiDavid Schlessinger
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shin YoshimotoMichihiko Ito
Feb 19, 2008·Genes & Development·Atsushi Suzuki, Yumiko Saga
Nov 6, 2008·Annual Review of Genetics·Jennifer A Marshall Graves
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Mark W MurphyVivian J Bardwell
Jul 22, 2011·Nature·Clinton K MatsonDavid Zarkower
May 26, 2012·Sexual Development : Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation·R JiménezM Burgos
Feb 8, 2013·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Andrew CuttingCraig A Smith
Mar 1, 2014·Developmental Biology·Luke S LambethCraig A Smith
May 27, 2014·Developmental Cell·Anna MinkinaDavid Zarkower
Jun 14, 2014·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Liang ZhaoPeter Koopman
Jul 31, 2014·Proceedings of the National Academy of Sciences of the United States of America·Liang ZhaoPeter Koopman

❮ Previous
Next ❯

Citations

Oct 16, 2015·Molecular Reproduction and Development·Denise Vizziano-CantonnetIrani Quagio-Grassiotto
May 26, 2015·Nature Structural & Molecular Biology·Mark W MurphyVivian J Bardwell
Jan 26, 2017·Developmental Biology·Liang ZhaoPeter Koopman
Jun 6, 2015·Biology of Reproduction·Charlotte Schubert
Dec 9, 2017·Fetal and Pediatric Pathology·Gizem Ürel DemirMehmet Alikaşifoğlu
May 18, 2018·Endocrine Reviews·Emmi RotgersHumphrey Hung-Chang Yao
Oct 12, 2018·Annual Review of Animal Biosciences·Mateus Contar AdolfiManfred Schartl
Aug 15, 2017·Nature Reviews. Genetics·Blanche Capel
Dec 28, 2018·Endocrine Reviews·Juho-Antti MäkeläJorma Toppari
Feb 6, 2016·Clinical Science·Ingrid KnarstonAndrew Sinclair
Apr 1, 2020·International Journal of Molecular Sciences·Nathalia Lisboa GomesRod T Mitchell
Dec 11, 2019·International Journal of Molecular Sciences·Romina P Grinspon, Rodolfo A Rey
Mar 10, 2019·Stem Cell Research & Therapy·Chenze XuMeijin Guo
Apr 30, 2017·Nature Reviews. Endocrinology·Hanna Katarina Lilith JohanssonJulie Boberg
Apr 7, 2020·Genetics and Molecular Biology·Kazuko FujitaniMichihiko Ito
Mar 20, 2019·Cellular and Molecular Life Sciences : CMLS·Wenteng HeShaorong Gao
Dec 29, 2020·The Journal of Clinical Endocrinology and Metabolism·Maristella SantiChrista E Flück
Dec 13, 2016·Developmental Biology·Kaitlyn A WebsterKellee R Siegfried
Mar 30, 2021·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Ji Won KimSung Han Shim
Apr 26, 2021·Hormones and Behavior·Ha Na Choe, Erich D Jarvis
Nov 13, 2020·Physiological Reviews·Yoshitaka NagahamaMasaru Nakamura
Jul 22, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Emmi RotgersHumphrey Hung-Chang Yao
Apr 26, 2019·Cells, Tissues, Organs·Ahmadreza RahaieShahin Eghbalsaied
Dec 18, 2021·Human Mutation·Ella ThomsonEmanuele Pelosi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Artificial Chromosomes

Artificial chromosomes are genetically engineered chromosomes derived from the DNA of a species. Discover the latest research on artificial chromosomes here.

Related Papers

Sexual Development : Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
Ryohei Sekido, R Lovell-Badge
Cellular and Molecular Life Sciences : CMLS
Satomi S Tanaka, Ryuichi Nishinakamura
© 2022 Meta ULC. All rights reserved