Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality - PubMed (original) (raw)

Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality

K Takeda et al. Proc Natl Acad Sci U S A. 1997.

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Disruption of the Stat3 gene. (a) The structure of the targeting vector and the mutated Stat3 gene. Restriction sites were: E, _Eco_RI; H, _Hin_dIII. (b) Southern blot analysis of the offspring from intercross of Stat3+/− mice. (c) PCR analysis of the microdissected embryonic tissues at E6.5. Primers a and b were used for detection of the wild-type allele, and a and c were used for the mutated allele.

Figure 2

Figure 2

Histological analysis of wild-type and Stat3−/− embryos. Wild-type embryos (a, c, e, and g) and Stat3−/− embryos (b, d, f, and h) were dissected at E6.0 (a and b), E6.5 (c and d), E7.0 (e and f), and E7.5 (g and h). Note the rapid degeneration of Stat3−/− embryos from E6.5 to E7.5. Stat3−/− embryos formed a two-layered egg cylinder at E6.0 (b) but were degenerated rapidly and resorbed completely by E7.5 (d, f, and h). ee, embryonic ectoderm; m, mesoderm; pac, proamniotic cavity; and ve, visceral endoderm. [Bars = 40 μm (a_–_f) and 100 μm (g and h).]

Figure 3

Figure 3

In vitro outgrowth of blastocysts. Blastocysts were cultured for 5 days, then photographed, lysed, and PCR-genotyped. (a) In vitro cultured wild-type blastocyst displaying outgrowth of trophoblast giant cells and ICM. (b) Cultured Stat3−/− blastocyst also displaying outgrowth of trophoblast giant cells and ICM, but the size of the ICM outgrowth was smaller than that of wild type. TG, trophoblast giant cell; ICM, inner cellular mass. (Bar = 40 μm.) (c) Graph of ICM outgrowth size. The shapes of ICM outgrowth were approximately ellipses, and surface areas were measured after 5 days of culture.

Similar articles

Cited by

References

    1. Schindler C, Darnell J E., Jr Annu Rev Biochem. 1995;64:621–651. - PubMed
    1. Ihle J N. Cell. 1996;84:331–334. - PubMed
    1. Meraz M A, White J M, Sheehan K C F, Bach E A, Rodig S J, Dighe A S, Kaplan D H, Riley J K, Greenlund A C, Campbell D, Carver-Moore K, DuBois R N, Clark R, Aguet M, Schreiber R D. Cell. 1996;84:431–442. - PubMed
    1. Durbin J E, Hackenmiller R, Simon M C, Levy D E. Cell. 1996;84:443–450. - PubMed
    1. Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T, Akira S. Nature (London) 1996;380:627–630. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources