Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis

Takehiro Arai, Jocelyn S. Kasper, Jeffrey R. Skaar, Syed Hamid Ali, Chiaki Takahashi, James A. DeCaprio

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)


Cul1, a member of the cullin ubiquitin ligase family, forms a multiprotein complex known as SCF and plays an essential role in numerous cellular and biological activities. A Cul1 homologue, p185 (Cul7), has been isolated as an simian virus 40 large T antigen-binding protein. To understand the physiological role of p185, we generated mice lacking p185. p185-/- embryos are runted and die immediately after birth because of respiratory distress. Dermal and hypodermal hemorrhage is detected in mutant embryos at late gestational stage. p185-/- placentas show defects in the differentiation of the trophoblast lineage with an abnormal vascular structure. We demonstrate that p185 forms an SCF-like complex with Skp1, Rbx1, Fbw6 (Fbx29), and FAP68 (FAP48, glomulin). FAP68 has recently been identified as a gene responsible for familial glomuvenous malformation. These results suggest that p185 forms a multiprotein complex and plays an important role in vascular morphogenesis.

Original languageEnglish
Pages (from-to)9855-9860
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
Publication statusPublished - Aug 19 2003

ASJC Scopus subject areas

  • General

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