| Loss of endothelial Tie1 receptor impairs lymphatic vessel development-brief report. | |
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MedLine Citation:
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PMID: 19910638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Studies of Tie1 gene-targeted embryos have demonstrated loss of blood vessel integrity, but the relevance of Tie1 in lymphatic vasculature development is unknown. We tested the hypothesis that the swelling observed in Tie1 mutant embryos is associated with lymphatic vascular defects. METHODS AND RESULTS: We could extend the survival of the Tie1-deficient embryos in the ICR background, which allowed us to study their lymphatic vessel development. At embryonic day (E) 14.5, the Tie1(-/-) embryos had edema and hemorrhages and began to die. Immunohistochemical analysis revealed that they have abnormal lymph sacs. Tie1(-/-) mutants were swollen already at E12.5 without signs of hemorrhage. Their lymph sacs were abnormally patterned, suggesting that lymphatic malformations precede the blood vascular defects. We generated mice with a conditional Cre/loxP Tie1(neo) locus and found that the homozygous Tie1(neo/neo) hypomorphic embryos survived until E15.5 with lymphatic malformations resembling those seen in the Tie1(-/-) mutants. CONCLUSIONS: Our data show that loss of Tie1 results in lymphatic vascular abnormalities that precede the blood vessel phenotype. These findings indicate that Tie1 is involved in lymphangiogenesis and suggest differential requirements for Tie1 signaling in the two vascular compartments. |
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Authors:
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Gabriela D'Amico; Emilia Anne Korhonen; Marika Waltari; Pipsa Saharinen; Pirjo Laakkonen; Kari Alitalo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-12 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-21 Completed Date: 2010-02-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 207-9 Citation Subset: IM |
Affiliation:
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Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, Department of Pathology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Edema / enzymology, physiopathology Embryo Loss Endothelial Cells / enzymology*, pathology Gestational Age Hemorrhage / enzymology, physiopathology Homozygote Immunohistochemistry Lymphangiogenesis* / genetics Lymphatic Vessels / embryology, enzymology*, physiopathology Mice Mice, Inbred ICR Mice, Knockout Phenotype Receptor, TIE-1 / deficiency, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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EC 2.7.10.1/Receptor, TIE-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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