Multifunctional reversible knockout/reporter system enabling fully functional reconstitution of the AML1/Runx1 locus and rescue of hematopoiesis.
Genesis
; 44(3): 115-21, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16496309
ABSTRACT
Mice deficient in the runt homology domain transcription factor Runx1 die of severe anemia in utero by embryonic day (E)12.5. A reactivatable Runx1 knockout embryonic stem cell (ESC) and mouse systems were generated by the targeted insertion of a loxP-flanked multipartite gene stop/trap cassette designed to simultaneously ablate the expression of Runx1 and report on the activity of its promoters. The cassette's in-frame LacZ reporter enabled activities of the proximal and the distal promoters to be differentially monitored. Although Runx1-null ESCs were capable of primitive erythroid differentiation in vitro, their capacity to generate granulocyte/macrophage or mixed myelo-erythroid embryoid bodies was lost. Cre-mediated reactivation restored Runx1 structural integrity and rescued the hematopoietic differentiation potential of ESCs. Mice with the reactivated allele survived, showed no hematopoietic deficit, and expressed all major splice isoforms of Runx1 appropriately. This multipurpose mouse model will be useful for the analysis of the critical Runx1-dependent check-point(s) in hematopoietic development.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Subunidade alfa 2 de Fator de Ligação ao Core
/
Hematopoese
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Genesis
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Reino Unido