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 and the biological relevance of Sp2 in the mouse are unknown.


RESULTS
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
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.
Baur
Frank
F
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany.
Nau
Kerstin
K
Sadic
Dennis
D
Allweiss
Lena
L
Elsässer
Hans-Peter
HP
Gillemans
Nynke
N
de Wit
Ton
T
Krüger
Imme
I
Vollmer
Marion
M
Philipsen
Sjaak
S
Suske
Guntram
G
D000818:Animals; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D051704:Sp2 Transcription Factor / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
D051704:Sp2 Transcription Factor; D004247:DNA