Change search
ReferencesLink to record
Permanent link

Direct link
Mice carrying a hypomorphic Evi1 allele are embryonic viable but exhibit severe congenital heart defects
Show others and affiliations
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2Article in journal (Refereed) Published
Abstract [en]

The ecotropic viral integration site 1 (Evi1) oncogenic transcription factor is one of a number of alternative transcripts encoded by the Mds1 and Evi1 complex locus (Mecom). Overexpression of Evi1 has been observed in a number of myeloid disorders and is associated with poor patient survival. It is also amplified and/or overexpressed in many epithelial cancers including nasopharyngeal carcinoma, ovarian carcinoma, ependymomas, and lung and colorectal cancers. Two murine knockout models have also demonstrated Evi1's critical role in the maintenance of hematopoietic stem cell renewal with its absence resulting in the death of mutant embryos due to hematopoietic failure. Here we characterize a novel mouse model (designated Evi1(fl3)) in which Evi1 exon 3, which carries the ATG start, is flanked by loxP sites. Unexpectedly, we found that germline deletion of exon3 produces a hypomorphic allele due to the use of an alternative ATG start site located in exon 4, resulting in a minor Evi1 N-terminal truncation and a block in expression of the Mds1-Evi1 fusion transcript. Evi1(δex3/δex3) mutant embryos showed only a mild non-lethal hematopoietic phenotype and bone marrow failure was only observed in adult Vav-iCre/+, Evi1(fl3/fl3) mice in which exon 3 was specifically deleted in the hematopoietic system. Evi1(δex3/δex3) knockout pups are born in normal numbers but die during the perinatal period from congenital heart defects. Database searches identified 143 genes with similar mutant heart phenotypes as those observed in Evi1(δex3/δex3) mutant pups. Interestingly, 42 of these congenital heart defect genes contain known Evi1-binding sites, and expression of 18 of these genes are also effected by Evi1 siRNA knockdown. These results show a potential functional involvement of Evi1 target genes in heart development and indicate that Evi1 is part of a transcriptional program that regulates cardiac development in addition to the development of blood.

Place, publisher, year, edition, pages
2014. Vol. 9, no 2
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-282514DOI: 10.1371/journal.pone.0089397ISI: 000332390800020PubMedID: 24586749OAI: diva2:917159
Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2016-04-07Bibliographically approved

Open Access in DiVA

fulltext(6403 kB)13 downloads
File information
File name FULLTEXT01.pdfFile size 6403 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ahmed, Sayadi
In the same journal
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 13 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 27 hits
ReferencesLink to record
Permanent link

Direct link