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Published on: April 2, 2014
Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality
1Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan.
Abstract:
Signal transducer and activator of transcription (STAT) proteins have been shown to mediate biological actions in response to cytokines. Stat3, a member of the STAT family, is activated by a variety of cytokines, including the interleukin 6 family of cytokines, leptin, granulocyte colony-stimulating factor, and epidermal growth factor. To address the biological function of Stat3, we generated mice deficient in Stat3 by gene targeting. No viable Stat3-deficient mice could be obtained from heterozygote intercross. Analysis of embryos at several gestation times revealed that Stat3-deficient embryos showed a rapid degeneration between embryonic days 6.5 and 7.5, although they developed into the egg cylinder stage until embryonic day 6.0. These results demonstrate that Stat3 is essential for the early development of mouse embryos.
Insights
Signal transducer and activator of transcription 3 (STAT3) is crucial for early embryonic development. Gene targeting revealed that Stat3-deficient mouse embryos degenerate early, highlighting its essential role in embryogenesis.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Signal transducer and activator of transcription (STAT) proteins mediate cellular responses to cytokines.
- STAT3 is activated by various cytokines like IL-6, leptin, G-CSF, and EGF.
- The precise biological function of STAT3 in early development remains to be fully elucidated.
Purpose of the Study:
- To investigate the essential biological function of STAT3 in early mouse embryonic development.
- To determine the consequences of STAT3 deficiency during embryogenesis.
Main Methods:
- Gene targeting was employed to generate mice deficient in STAT3.
- Heterozygote intercrosses were performed to obtain STAT3-deficient offspring.
- Embryos were analyzed at various gestational stages (up to embryonic day 7.5).
Main Results:
- No viable STAT3-deficient mice were obtained from heterozygote intercrosses.
- STAT3-deficient embryos developed until the egg cylinder stage (embryonic day 6.0).
- Rapid degeneration of STAT3-deficient embryos occurred between embryonic days 6.5 and 7.5.
Conclusions:
- STAT3 is indispensable for the successful progression of early mouse embryonic development.
- The absence of STAT3 leads to embryonic lethality due to developmental failure.
- These findings underscore the critical role of STAT3 signaling in embryogenesis.
