DOI: 10.1242/dev.126.8.1631. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects

Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects

10.1242/dev.126.8.1631

Crossref journal-article

The Company of Biologists

Development (237)

Abstract

Abstract Smad5 has been implicated as a downstream signal mediator for several bone morphogenetic proteins (BMPs). To understand the in vivo function of Smad5, we generated mice deficient in Smad5 using embryonic stem (ES) cell technology. Homozygous mutant embryos die between E9.5 and E11.5, and display variable phenotypes. Morphological defects are first detected at E8.0 in the developing amnion, gut and heart (the latter defect being similar to BMP-2 knockout mice). At later stages, mutant embryos fail to undergo proper turning, have craniofacial and neural tube abnormalities, and are edematous. In addition, several extraembryonic lesions are observed. After E9.0, the yolk sacs of the mutants contain red blood cells but lack a well-organized vasculature, which is reminiscent of BMP-4, TGF-β1 and TGF-β type II receptor knockout mice. In addition, the allantois of many Smad5 mutants is fused to the chorion, but is not well-elongated. A unique feature of the Smad5 mutant embryos is that ectopic vasculogenesis and hematopoiesis is observed in the amnion, likely due to mislocation of allantois tissue. Despite the expression of Smad5 from gastrulation onwards, and in contrast to knockouts of Smad2 and Smad4, Smad5 only becomes essential later in extraembryonic and embryonic development.

Bibliography

Chang, H., Huylebroeck, D., Verschueren, K., Guo, Q., Matzuk, M. M., & Zwijsen, A. (1999). Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development, 126(8), 1631â1642.

Authors 6

Hua Chang (first)
Danny Huylebroeck (additional)
Kristin Verschueren (additional)
Qiuxia Guo (additional)
Martin M. Matzuk (additional)
An Zwijsen (additional)

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Dates

Type	When
Created	4 years, 4 months ago (April 25, 2021, 11:59 p.m.)
Deposited	2 years ago (Sept. 5, 2023, 12:26 p.m.)
Indexed	1 month ago (Aug. 3, 2025, 12:37 a.m.)
Issued	26 years, 4 months ago (April 15, 1999)
Published	26 years, 4 months ago (April 15, 1999)
Published Online	26 years, 4 months ago (April 15, 1999)
Published Print	26 years, 4 months ago (April 15, 1999)

Funders 0

None

BibTeX

@article{Chang_1999, title={Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects}, volume={126}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.126.8.1631}, DOI={10.1242/dev.126.8.1631}, number={8}, journal={Development}, publisher={The Company of Biologists}, author={Chang, Hua and Huylebroeck, Danny and Verschueren, Kristin and Guo, Qiuxia and Matzuk, Martin M. and Zwijsen, An}, year={1999}, month=apr, pages={1631–1642} }

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