Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.

In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD) have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase...

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Autores principales:	Nick Warr, Debora Bogani, Pam Siggers, Rachel Brixey, Hilda Tateossian, Asha Dopplapudi, Sara Wells, Michael Cheeseman, Ying Xia, Harry Ostrer, Andy Greenfield
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/90c4c456a12b4bcdaab8107f57443116
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spelling	oai:doaj.org-article:90c4c456a12b4bcdaab8107f574431162021-11-18T06:54:32ZMinor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.1932-620310.1371/journal.pone.0019572https://doaj.org/article/90c4c456a12b4bcdaab8107f574431162011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21559298/?tool=EBIhttps://doaj.org/toc/1932-6203In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD) have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase kinase 1, MAP3K1, a component of the mitogen-activated protein kinase (MAPK) signal transduction pathway. In individuals harbouring heterozygous mutations in MAP3K1, dysregulation of MAPK signalling was observed in lymphoblastoid cell lines, suggesting a causal role for these mutations in disrupting XY sexual development. Mice lacking the cognate gene, Map3k1, are viable and exhibit the eyes open at birth (EOB) phenotype on a mixed genetic background, but on the C57BL/6J genetic background most mice die at around 14.5 dpc due to a failure of erythropoiesis in the fetal liver. However, no systematic examination of sexual development in Map3k1-deficient mice has been described, an omission that is especially relevant in the case of C57BL/6J, a genetic background that is sensitized to disruptions to testis determination. Here, we report that on a mixed genetic background mice lacking Map3k1 are fertile and exhibit no overt abnormalities of testis development. On C57BL/6J, significant non-viability is observed with very few animals surviving to adulthood. However, an examination of development in Map3k1-deficient XY embryos on this genetic background revealed no significant defects in testis determination, although minor abnormalities were observed, including an increase in gonadal length. Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans.Nick WarrDebora BoganiPam SiggersRachel BrixeyHilda TateossianAsha DopplapudiSara WellsMichael CheesemanYing XiaHarry OstrerAndy GreenfieldPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19572 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nick Warr Debora Bogani Pam Siggers Rachel Brixey Hilda Tateossian Asha Dopplapudi Sara Wells Michael Cheeseman Ying Xia Harry Ostrer Andy Greenfield Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.
description	In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD) have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase kinase 1, MAP3K1, a component of the mitogen-activated protein kinase (MAPK) signal transduction pathway. In individuals harbouring heterozygous mutations in MAP3K1, dysregulation of MAPK signalling was observed in lymphoblastoid cell lines, suggesting a causal role for these mutations in disrupting XY sexual development. Mice lacking the cognate gene, Map3k1, are viable and exhibit the eyes open at birth (EOB) phenotype on a mixed genetic background, but on the C57BL/6J genetic background most mice die at around 14.5 dpc due to a failure of erythropoiesis in the fetal liver. However, no systematic examination of sexual development in Map3k1-deficient mice has been described, an omission that is especially relevant in the case of C57BL/6J, a genetic background that is sensitized to disruptions to testis determination. Here, we report that on a mixed genetic background mice lacking Map3k1 are fertile and exhibit no overt abnormalities of testis development. On C57BL/6J, significant non-viability is observed with very few animals surviving to adulthood. However, an examination of development in Map3k1-deficient XY embryos on this genetic background revealed no significant defects in testis determination, although minor abnormalities were observed, including an increase in gonadal length. Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans.
format	article
author	Nick Warr Debora Bogani Pam Siggers Rachel Brixey Hilda Tateossian Asha Dopplapudi Sara Wells Michael Cheeseman Ying Xia Harry Ostrer Andy Greenfield
author_facet	Nick Warr Debora Bogani Pam Siggers Rachel Brixey Hilda Tateossian Asha Dopplapudi Sara Wells Michael Cheeseman Ying Xia Harry Ostrer Andy Greenfield
author_sort	Nick Warr
title	Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.
title_short	Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.
title_full	Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.
title_fullStr	Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.
title_full_unstemmed	Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.
title_sort	minor abnormalities of testis development in mice lacking the gene encoding the mapk signalling component, map3k1.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/90c4c456a12b4bcdaab8107f57443116
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Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.

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