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BOR - Papers in Press, published online ahead of print August 27, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.070409
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BIOLOGY OF REPRODUCTION 79, 1014–1020 (2008)
DOI: 10.1095/biolreprod.108.070409
© 2008 by the Society for the Study of Reproduction, Inc.

Oocyte-Specific Knockout: A Novel In Vivo Approach for Studying Gene Functions During Folliculogenesis, Oocyte Maturation, Fertilization, and Embryogenesis1

Qing-Yuan Sun 3 4, Kui Liu 5, and Kazuhiro Kikuchi 2 4

State Key Laboratory of Reproductive Biology,3 Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China Division of Animal Sciences,4 National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602, Japan Department of Medical Biochemistry and Biophysics,5 Umeå University, SE-901 87 Umeå, Sweden

ABSTRACT

Knockout mice have been highly useful tools in helping to understand the functional roles of specific genes in development and diseases. However, in many cases, knockout mice are embryonic lethal, which prevents investigation into a number of important questions, or they display developmental abnormalities, including fertility defects. In contrast, conditional knockout, which is achieved by the Cre-LoxP system, can be used to delete a gene in a specific organ or tissue, or at a specific developmental stage. This technique has advantages over conventional knockout, especially when conventional knockout causes embryonic lethality or when the function of maternal transcripts in early development needs to be defined. Recently, a widely used practice has been used to specifically delete genes of interest in oocytes: Zp3-Cre or Gdf9-Cre transgenic mouse lines, in which Cre-recombinase expression is driven by oocyte-specific zona pellucida 3 (Zp3) promoter or growth differentiation factor 9 (Gdf9) promoter, are crossed with mice bearing floxed target genes. This novel in vivo approach has helped to increase the understanding of the functions of specific genes in folliculogenesis/oogenesis, oocyte maturation, fertilization, and embryogenesis. In this minireview we discuss recent advances in understanding the molecular mechanisms regulating major reproductive and developmental events as revealed by oocyte-specific conditional knockout and perspectives on this technology and related studies.

conditional knockout, Cre-recombinase, embryo, embryogenesis, fertilization, follicular development, folliculogenesis, gamete biology, meiosis, oocyte


FOOTNOTES

1This work was completed when Q.-Y.S. worked in Kazuhiro Kikuchi's laboratory supported by an Invitation Fellowship for Research from the Japanese Society for the Promotion of Science (JSPS-S08127). Q.-Y.S. is currently supported by the National Basic Research Program of China (2006CB944001 and 2006CB504004).

Correspondence: 2Kazuhiro Kikuchi, Division of Animal Sciences, National Institute of Agrobiological Sciences, Kannondai 2-1-2, Tsukuba, Ibaraki 305-8602, Japan. FAX: 81 298 38 7447; e-mail: kiku{at}affrc.go.jp







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