Dicer is required for embryonic angiogenesis during mouse development

Wei J. Yang, Derek D. Yang, Songqing Na, George Sandusky, Qing Zhang, Genshi Zhao

Research output: Contribution to journalArticle

391 Citations (Scopus)

Abstract

Dicer is a multi-domain protein responsible for the generation of short interfering RNAs (siRNAs) from long double-stranded RNAs during RNA interference. It is also involved in the maturation of microRNAs, some of which are transcriptional regulators of developmental timing in nematodes. To assess the role of Dicer in mammals, we generated Dicerex1/2 mice with a deletion of the amino acid sequences corresponding to the first and second exons of the dicer gene via homologous recombination. We found that Dicer ex1/2 homozygous embryos displayed a retarded phenotype and died between days 12.5 and 14.5 of gestation. Thus, these results show that dicerex1/2 is severely hypomorphic and that Dicer is essential for normal mouse development. Interestingly, we also found that blood vessel formation/maintenance in dicerex1/2 embryos and yolk sacs were severely compromised, suggesting a possible role for Dicer in angiogenesis. This finding is consistent with the altered expression of vegf, flt1, kdr, and tie1 in the mutant embryos. Taken together, the results of this study indicate that Dicer exerts its function on mouse embryonic angiogenesis probably through its role in the processing of microRNAs that regulate the expression levels of some critical angiogenic regulators in the cell.

Original languageEnglish (US)
Pages (from-to)9330-9335
Number of pages6
JournalJournal of Biological Chemistry
Volume280
Issue number10
DOIs
StatePublished - Mar 11 2005
Externally publishedYes

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MicroRNAs
Embryonic Structures
Mammals
Double-Stranded RNA
Blood vessels
Vascular Endothelial Growth Factor A
Small Interfering RNA
Exons
Yolk Sac
Genes
Homologous Recombination
RNA
RNA Interference
Amino Acids
Blood Vessels
Amino Acid Sequence
Processing
Maintenance
Phenotype
Pregnancy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dicer is required for embryonic angiogenesis during mouse development. / Yang, Wei J.; Yang, Derek D.; Na, Songqing; Sandusky, George; Zhang, Qing; Zhao, Genshi.

In: Journal of Biological Chemistry, Vol. 280, No. 10, 11.03.2005, p. 9330-9335.

Research output: Contribution to journalArticle

Yang, Wei J. ; Yang, Derek D. ; Na, Songqing ; Sandusky, George ; Zhang, Qing ; Zhao, Genshi. / Dicer is required for embryonic angiogenesis during mouse development. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 10. pp. 9330-9335.
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