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Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition

Nature Genetics volume 33, pages 187–191 (2003)Cite this article

Abstract

The female gamete (the oocyte) serves the distinct purpose of transmitting the maternal genome and other maternal factors that are critical for post-ovulation events1,2,3,4. Through the identification and characterization of oocyte-specific factors, we are beginning to appreciate the diverse functions of oocytes in ovarian folliculogenesis, fertilization and embryogenesis5,6. To understand these processes further, we identified genes called zygote arrest 1 (Zar1 and ZAR1 in mouse and human, respectively) as novel oocyte-specific genes. These encode proteins of 361 amino acids and 424 amino acids, respectively, which share 59% amino-acid identity and an atypical plant homeo-domain (PHD) motif7. Although Zar1-null (Zar1−/−) mice are viable and grossly normal, Zar1−/− females are infertile. Ovarian development and oogenesis through the early stages of fertilization are evidently unimpaired, but most embryos from Zar1−/− females arrest at the one-cell stage. Distinct pronuclei form and DNA replication initiates, but the maternal and paternal genomes remain separate in arrested zygotes. Fewer than 20% of the embryos derived from Zar1−/− females progress to the two-cell stage and show marked reduction in the synthesis of the transcription-requiring complex8, and no embryos develop to the four-cell stage. Thus, Zar1 is the first identified oocyte-specific maternal-effect gene that functions at the oocyte-to-embryo transition and, as such, offers new insights into the initiation of embryonic development and fertility control in mammals.

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Figure 1: Comparison of human ZAR1 and mouse Zar1 amino-acid sequences.
Figure 2: Expression analysis of zygote arrest 1 in mouse and human tissues.
Figure 3: Localization of Zar1 in mouse ovaries.
Figure 4: Targeting strategy of Zar1 and Southern-blot and northern-blot analyses of F2 offspring.
Figure 5: Zar1 expression.
Figure 6: Development of embryos derived from Zar1+/− and Zar1−/− mice.

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Acknowledgements

We thank M. Berry, R. Burgess, K. Burns, T. Gridley, G. Kopf and T. Kumar for critical review of the manuscript, S. Baker for aid in manuscript formatting and C. Brown, K. Burns, L. Chen, L. Erdos, M. O'Brien, P. Wang and C. Yan for technical assistance. These studies were supported in part by a sponsored research grant from Wyeth Research and US National Institutes of Health grants (to M.M.M. and J.J.E.). X. Wu was supported in part by a post-doctoral fellowship from the Lalor Foundation.

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  1. Maria M. Viveiros

    Present address: The Center for Transgenesis and Germ Cell Research, Department of Animal Biology, University of Pennsylvania, Kennet Square, Pennsylvania, USA

Authors and Affiliations

  1. Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, USA

    Xuemei Wu & Martin M. Matzuk

  2. The Jackson Laboratory, Bar Harbor, Maine, USA

    Maria M. Viveiros & John J. Eppig

  3. Wyeth Research, Collegeville, Pennsylvania, USA

    Yuchen Bai & Susan L. Fitzpatrick

  4. Departments of Molecular and Cellular Biology and of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

    Martin M. Matzuk

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Correspondence to Martin M. Matzuk.

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This work was supported by a grant from Wyeth Research as described in the Acknowledgments.

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Wu, X., Viveiros, M., Eppig, J. et al. Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition. Nat Genet 33, 187–191 (2003). https://doi.org/10.1038/ng1079

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