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

Nat Genet. 2003 Feb;33(2):187-91. doi: 10.1038/ng1079. Epub 2003 Jan 21.


The female gamete (the oocyte) serves the distinct purpose of transmitting the maternal genome and other maternal factors that are critical for post-ovulation events. Through the identification and characterization of oocyte-specific factors, we are beginning to appreciate the diverse functions of oocytes in ovarian folliculogenesis, fertilization and embryogenesis. 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) motif. 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 complex, 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Blotting, Western
  • Cloning, Molecular
  • DNA Replication
  • Egg Proteins / physiology*
  • Embryo, Mammalian / physiology*
  • Female
  • Fertility / physiology
  • Fertilization in Vitro
  • Gene Expression Regulation
  • Gene Library
  • Goats
  • In Vitro Techniques
  • Male
  • Meiosis
  • Mice / embryology*
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oocytes / physiology*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Spermatids / physiology*
  • Stem Cells / physiology
  • Zygote / metabolism*


  • Egg Proteins
  • RNA, Messenger
  • Zar1 protein, human
  • Zar1 protein, mouse

Associated data

  • GENBANK/AY191415
  • GENBANK/AY191416
  • GENBANK/AY193889
  • GENBANK/AY193890