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First published online 1 September 2004
doi: 10.1242/dev.01336
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1 Laboratory of Signal Transduction, National Institute of Environmental Health
Science, National Institutes of Health, Department of Health and Human
Services, Research Triangle Park, NC 27709, USA
2 Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC
27710, USA
3 The Office of Clinical Research, National Institute of Environmental Health
Science, National Institutes of Health, Department of Health and Human
Services, Research Triangle Park, NC 27709, USA
4 Department of Medicine, Duke University Medical Center, Durham, NC 27710,
USA
5 Department of Biochemistry, Duke University Medical Center, Durham, NC 27710,
USA
* Author for correspondence (e-mail: black009{at}niehs.nih.gov)
Accepted 28 June 2004
The CCCH tandem zinc finger protein, Zfp36l2, like its better-known
relative tristetraprolin (TTP), can decrease the stability of AU-rich
element-containing transcripts in cell transfection studies; however, its
physiological importance is unknown. We disrupted Zfp36l2 in mice,
resulting in decreased expression of a truncated protein in which the
N-terminal 29 amino acids had been deleted (
N-Zfp36l2). Mice derived
from different clones of ES cells exhibited complete female infertility,
despite evidence from embryo and ovary transplantation experiments that they
could gestate and rear wild-type young. N-Zfp36l2 females apparently
cycled and ovulated normally, and their ova could be fertilized; however, the
embryos did not progress beyond the two-cell stage of development. These mice
represent a specific model of disruption of the earliest stages of
embryogenesis, implicating Zfp36l2, a probable mRNA-binding and destabilizing
protein, in the physiological control of female fertility at the level of
early embryonic development. This newly identified biological role for Zfp36l2
may have implications for maternal mRNA turnover in normal embryogenesis, and
conceivably could be involved in some cases of unexplained human female
infertility.
Key words: Female fertility, Early embryonic development, CCCH tandem zinc-finger proteins
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