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The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders
A spontaneous mutation leading to the formation of congenital ovarian and testicular tumors was detected in the WKY/Ztm rat strain. The histological evaluation revealed derivatives from all three germ layers, thereby identifying these tumors as teratomas. Teratocarcinogenesis was accompanied by infe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360017/ https://www.ncbi.nlm.nih.gov/pubmed/22655094 http://dx.doi.org/10.1371/journal.pone.0038001 |
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author | Northrup, Emily Zschemisch, Nils-Holger Eisenblätter, Regina Glage, Silke Wedekind, Dirk Cuppen, Edwin Dorsch, Martina Hedrich, Hans-Jürgen |
author_facet | Northrup, Emily Zschemisch, Nils-Holger Eisenblätter, Regina Glage, Silke Wedekind, Dirk Cuppen, Edwin Dorsch, Martina Hedrich, Hans-Jürgen |
author_sort | Northrup, Emily |
collection | PubMed |
description | A spontaneous mutation leading to the formation of congenital ovarian and testicular tumors was detected in the WKY/Ztm rat strain. The histological evaluation revealed derivatives from all three germ layers, thereby identifying these tumors as teratomas. Teratocarcinogenesis was accompanied by infertility and the underlying mutation was termed ter. Linkage analysis of 58 (WKY-ter×SPRD-Cu3) F2 rats associated the ter mutation with RNO18 (LOD = 3.25). Sequencing of candidate genes detected a point mutation in exon 4 of the dead-end homolog 1 gene (Dnd1), which introduces a premature stop codon assumed to cause a truncation of the Dnd1 protein. Genotyping of the recessive ter mutation revealed a complete penetrance of teratocarcinogenesis and infertility in homozygous ter rats of both genders. Morphologically non-tumorous testes of homozygous ter males were reduced in both size and weight. This testicular malformation was linked to a lack of spermatogenesis using immunohistochemical and histological staining. Our WKY-Dnd1(ter)/Ztm rat is a novel animal model to investigate gonadal teratocarcinogenesis and the molecular mechanisms involved in germ cell development of both genders. |
format | Online Article Text |
id | pubmed-3360017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33600172012-05-31 The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders Northrup, Emily Zschemisch, Nils-Holger Eisenblätter, Regina Glage, Silke Wedekind, Dirk Cuppen, Edwin Dorsch, Martina Hedrich, Hans-Jürgen PLoS One Research Article A spontaneous mutation leading to the formation of congenital ovarian and testicular tumors was detected in the WKY/Ztm rat strain. The histological evaluation revealed derivatives from all three germ layers, thereby identifying these tumors as teratomas. Teratocarcinogenesis was accompanied by infertility and the underlying mutation was termed ter. Linkage analysis of 58 (WKY-ter×SPRD-Cu3) F2 rats associated the ter mutation with RNO18 (LOD = 3.25). Sequencing of candidate genes detected a point mutation in exon 4 of the dead-end homolog 1 gene (Dnd1), which introduces a premature stop codon assumed to cause a truncation of the Dnd1 protein. Genotyping of the recessive ter mutation revealed a complete penetrance of teratocarcinogenesis and infertility in homozygous ter rats of both genders. Morphologically non-tumorous testes of homozygous ter males were reduced in both size and weight. This testicular malformation was linked to a lack of spermatogenesis using immunohistochemical and histological staining. Our WKY-Dnd1(ter)/Ztm rat is a novel animal model to investigate gonadal teratocarcinogenesis and the molecular mechanisms involved in germ cell development of both genders. Public Library of Science 2012-05-24 /pmc/articles/PMC3360017/ /pubmed/22655094 http://dx.doi.org/10.1371/journal.pone.0038001 Text en Northrup et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Northrup, Emily Zschemisch, Nils-Holger Eisenblätter, Regina Glage, Silke Wedekind, Dirk Cuppen, Edwin Dorsch, Martina Hedrich, Hans-Jürgen The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders |
title | The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders |
title_full | The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders |
title_fullStr | The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders |
title_full_unstemmed | The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders |
title_short | The ter Mutation in the Rat Dnd1 Gene Initiates Gonadal Teratomas and Infertility in Both Genders |
title_sort | ter mutation in the rat dnd1 gene initiates gonadal teratomas and infertility in both genders |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360017/ https://www.ncbi.nlm.nih.gov/pubmed/22655094 http://dx.doi.org/10.1371/journal.pone.0038001 |
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