Faculty Collaboration Database

Absence of the blood-clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Proc Natl Acad Sci U S A 1995 Jan 31;92(3):850-4

Date

01/31/1995

Pubmed ID

7846065

Pubmed Central ID

PMC42718

DOI

10.1073/pnas.92.3.850

Scopus ID

2-s2.0-0028876697 (requires institutional sign-in at Scopus site)   224 Citations

Abstract

We have targeted the murine thrombomodulin (TM) gene in embryonic stem cells and generated embryos as well as mice with TM deficiency. The heterozygous TM-deficient (TM+/-) mice as compared to wild-type (TM+/+) littermates exhibit 50% reductions in the levels of TM mRNA and TM protein. However, TM+/- mice appear normal and are free of thrombotic complications. The homozygous TM-deficient (TM-/-) embryos die before embryonic day 9.5. An overall retardation in growth and development of TM-/- embryos is first evident on embryonic day 8.5 (8-12 somite pairs). However, no specific pathologic abnormalities are observed. These initial changes take place at a time when TM is normally expressed in the parietal yolk sac. The removal of embryonic day 7.5 TM-/- embryos from maternal decidua and their subsequent culture in vitro allow development to proceed to stages not observed in vivo (13-20 somite pairs) with the appearance of normal blood vessels in the visceral yolk sac and embryo. The results of our studies suggest that the failure of TM-/- embryos to survive at mid-gestation is a consequence of dysfunctional maternal-embryonic interactions caused by the absence of TM in the parietal yolk sac and demonstrate that the receptor is necessary for normal embryonic development in utero.

Author List

Healy AM, Rayburn HB, Rosenberg RD, Weiler H

Author

Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Cardiovascular System
Chimera
Crosses, Genetic
Embryonic and Fetal Development
Female
Gene Targeting
Genes, Lethal
Male
Mice
Molecular Sequence Data
Mutation
RNA, Messenger
Stem Cells
Thrombomodulin