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The  Nczf  gene has been identified as one of Ncx target genes and encodes a novel KRAB zinc-finger protein, which functions as a sequence specific transcriptional repressor. In order to elucidate Nczf functions, we generated Nczf knockout (Nczf−/−) mice. Nczf−/− mice died around embryonic day 8.5 (E8.5) with small body size and impairment of axial rotation. Histopathological analysis revealed that the cell number decreased and pyknotic cells were occasionally observed. We examined the expression of cell cycle related genes in Nczf−/− mice.  p27  expression was increased in E8.0 Nczf−/− mice compared to that of wild type mice. Nczf knockdown by siRNA resulted in increased expression of  p27  in mouse embryonic fibroblasts (MEFs). Furthermore,  p27  promoter luciferase reporter gene analysis confirmed the regulation of  p27  mRNA expression by Nczf. Nczf−/−; p27−/− double knockout mice survived until E11.5 and the defect of axial rotation was restored. These data suggest that  p27  repression by Nczf is essential in the developing embryo.

Transcriptional repression of p27 is essential for murine embryonic development