title: Sp1/Sp3 compound heterozygous mice are not viable: impaired erythropoiesis and severe placental defects.
abstract: The ubiquitously expressed zinc finger transcription factors Sp1 and Sp3 play critical roles in embryonic development. Sp1 knockout mice die around embryonic day 10.5. Mice lacking Sp3 are postnatal lethal. Mice heterozygous for either Sp1 or Sp3 are apparently normal, although slightly smaller. Here, we show that compound heterozygosity of Sp1 and Sp3 results in embryonic lethality accompanied by a spectrum of developmental abnormalities, including growth retardation, morphological alterations of the lung, impaired ossification, anemia, and placental defects. Anemia in Sp1/Sp3 compound heterozygous mutant embryos is associated with impaired maturation of erythrocytes. Analyses of the placenta revealed a markedly reduced spongiotrophoblast layer and a severe disorganization of the labyrinth layer in Sp1/Sp3 compound heterozygous as well as in Sp3-deficient mutant embryos. Our findings demonstrate that a threshold of Sp1 and Sp3 activity is required for normal embryonic development, suggesting that Sp1 and Sp3 act cooperatively to regulate downstream targets.
authors.affiliation: Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Imme
authors.initials: I
authors.lastname: Krüger
authors.forename: Marion
authors.initials: M
authors.lastname: Vollmer
authors.forename: David G
authors.initials: DG
authors.lastname: Simmons
authors.forename: David
authors.initials: D
authors.lastname: Simmons
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Elsässer
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
authors.forename: Guntram
authors.initials: G
authors.lastname: Suske
mesh_terms: D000818:Animals; D004920:Erythropoiesis / Q000235:genetics*; D006579:Heterozygote; D051379:Mice; D010641:Phenotype; D010920:Placenta / Q000002:abnormalities* / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000172:deficiency / Q000235:genetics*; D051705:Sp3 Transcription Factor / Q000172:deficiency / Q000235:genetics*; D015996:Survival Rate
chemical_list: D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor