Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts.
BACKGROUND: The zinc finger protein Sp2 (specificity protein 2) is a member of the glutamine-rich Sp family of transcription factors. Despite its close similarity to Sp1, Sp3 and Sp4, Sp2 does not bind to DNA or activate transcription when expressed in mammalian cell lines. The expression pattern an...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2010-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC2833205?pdf=render |
_version_ | 1818911902880759808 |
---|---|
author | Frank Baur Kerstin Nau Dennis Sadic Lena Allweiss Hans-Peter Elsässer Nynke Gillemans Ton de Wit Imme Krüger Marion Vollmer Sjaak Philipsen Guntram Suske |
author_facet | Frank Baur Kerstin Nau Dennis Sadic Lena Allweiss Hans-Peter Elsässer Nynke Gillemans Ton de Wit Imme Krüger Marion Vollmer Sjaak Philipsen Guntram Suske |
author_sort | Frank Baur |
collection | DOAJ |
description | BACKGROUND: The zinc finger protein Sp2 (specificity protein 2) is a member of the glutamine-rich Sp family of transcription factors. Despite its close similarity to Sp1, Sp3 and Sp4, Sp2 does not bind to DNA or activate transcription when expressed in mammalian cell lines. The expression pattern and the biological relevance of Sp2 in the mouse are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Whole-mount in situ hybridization of mouse embryos between E7.5 and E9.5 revealed abundant expression in most embryonic and extra-embryonic tissues. In order to unravel the biological relevance of Sp2, we have targeted the Sp2 gene by a tri-loxP strategy. Constitutive Sp2null and conditional Sp2cko knockout alleles were obtained by crossings with appropriate Cre recombinase expressing mice. Constitutive disruption of the mouse Sp2 gene (Sp2null) resulted in severe growth retardation and lethality before E9.5. Mouse embryonic fibroblasts (MEFs) derived from Sp2null embryos at E9.5 failed to grow. Cre-mediated ablation of Sp2 in Sp2cko/cko MEFs obtained from E13.5 strongly impaired cell proliferation. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Sp2 is essential for early mouse development and autonomous proliferation of MEFs in culture. Comparison of the Sp2 knockout phenotype with the phenotypes of Sp1, Sp3 and Sp4 knockout strains shows that, despite their structural similarity and evolutionary relationship, all four glutamine-rich members of the Sp family of transcription factors have distinct non-redundant functions in vivo. |
first_indexed | 2024-12-19T23:06:05Z |
format | Article |
id | doaj.art-9310873f1b3943e4bef3e5cde6692409 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-19T23:06:05Z |
publishDate | 2010-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-9310873f1b3943e4bef3e5cde66924092022-12-21T20:02:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0153e958710.1371/journal.pone.0009587Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts.Frank BaurKerstin NauDennis SadicLena AllweissHans-Peter ElsässerNynke GillemansTon de WitImme KrügerMarion VollmerSjaak PhilipsenGuntram SuskeBACKGROUND: The zinc finger protein Sp2 (specificity protein 2) is a member of the glutamine-rich Sp family of transcription factors. Despite its close similarity to Sp1, Sp3 and Sp4, Sp2 does not bind to DNA or activate transcription when expressed in mammalian cell lines. The expression pattern and the biological relevance of Sp2 in the mouse are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Whole-mount in situ hybridization of mouse embryos between E7.5 and E9.5 revealed abundant expression in most embryonic and extra-embryonic tissues. In order to unravel the biological relevance of Sp2, we have targeted the Sp2 gene by a tri-loxP strategy. Constitutive Sp2null and conditional Sp2cko knockout alleles were obtained by crossings with appropriate Cre recombinase expressing mice. Constitutive disruption of the mouse Sp2 gene (Sp2null) resulted in severe growth retardation and lethality before E9.5. Mouse embryonic fibroblasts (MEFs) derived from Sp2null embryos at E9.5 failed to grow. Cre-mediated ablation of Sp2 in Sp2cko/cko MEFs obtained from E13.5 strongly impaired cell proliferation. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Sp2 is essential for early mouse development and autonomous proliferation of MEFs in culture. Comparison of the Sp2 knockout phenotype with the phenotypes of Sp1, Sp3 and Sp4 knockout strains shows that, despite their structural similarity and evolutionary relationship, all four glutamine-rich members of the Sp family of transcription factors have distinct non-redundant functions in vivo.http://europepmc.org/articles/PMC2833205?pdf=render |
spellingShingle | Frank Baur Kerstin Nau Dennis Sadic Lena Allweiss Hans-Peter Elsässer Nynke Gillemans Ton de Wit Imme Krüger Marion Vollmer Sjaak Philipsen Guntram Suske Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts. PLoS ONE |
title | Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts. |
title_full | Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts. |
title_fullStr | Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts. |
title_full_unstemmed | Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts. |
title_short | Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts. |
title_sort | specificity protein 2 sp2 is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts |
url | http://europepmc.org/articles/PMC2833205?pdf=render |
work_keys_str_mv | AT frankbaur specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT kerstinnau specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT dennissadic specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT lenaallweiss specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT hanspeterelsasser specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT nynkegillemans specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT tondewit specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT immekruger specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT marionvollmer specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT sjaakphilipsen specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts AT guntramsuske specificityprotein2sp2isessentialformousedevelopmentandautonomousproliferationofmouseembryonicfibroblasts |