Abstract
Zfp148 belongs to a large family of C2H2-type zinc-finger transcription factors. Zfp148 is expressed in fetal germ cells in 13.5-d-old (E13.5) mouse embryos. Germ-line transmission of mutations were not observed in chimeric Zfp148+/− mice, and some of these mice completely lacked spermatogonia. The number of primordial germ cells in Zfp148+/− tetraploid embryos was normal until E11.5, but declined from E11.5 to E13.5 and continued to decline until few germ cells were present at E18.5. This phenotype was not rescued by wild-type Sertoli or stromal cells, and is therefore a cell-autonomous phenotype. These results indicate that two functional alleles of Zfp148 are required for the normal development of fetal germ cells. Recent studies have shown that Zfp148 activates p53, which has an important role in cell-cycle regulation1. Primordial germ cells stop proliferating at approximately E13.5, which correlates with induction of phosphorylation of p53 and its translocation to the nucleus. Phosphorylation of p53 is impaired in Zfp148+/− embryonic stem cells and in fetal germ cells from chimeric Zfp148+/− embryos. Thus, Zfp148 may be required for regulating p53 in the development of germ cells.
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Acknowledgements
We thank E.M. Eddy, G.-Q. Zhao, Y. Matsui, P. Koopman and R. Newbold for helpful discussion; R. Behringer and A. Bradley for use of AB-1 ES cells; T. Castranio for advice on production of tetraploid chimeras; M. Suzuki for technical advice on blastocyst injection; T.C., G. Scott and S. Kishigami for critical reading of the manuscript; S. Ito for helping experiment of chromosomal count of ES cells; and Y. Takeuchi, Y. and K. Mishina and Chata for encouragement. This study was supported by the Fund for Comprehensive Research on Aging and Health.
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Takeuchi, A., Mishina, Y., Miyaishi, O. et al. Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells during mouse embryogenesis. Nat Genet 33, 172–176 (2003). https://doi.org/10.1038/ng1072
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DOI: https://doi.org/10.1038/ng1072
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