Abstract
The CBFbeta subunit is the non-DNA-binding subunit of the heterodimeric core-binding factor (CBF). CBFbeta associates with DNA-binding CBFalpha subunits and increases their affinity for DNA. Genes encoding the CBFbeta subunit (CBFB) and one of the CBFalpha subunits (CBFA2, otherwise known as AML1) are the most frequent targets of chromosomal translocations in acute leukemias in humans. We and others previously demonstrated that homozygous disruption of the mouse Cbfa2 (AML1) gene results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system and blocks fetal liver hematopoiesis. Here we demonstrate that homozygous mutation of the Cbfb gene results in the same phenotype. Our results demonstrate that the CBFbeta subunit is required for CBFalpha2 function in vivo.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alleles
-
Animals
-
Blood Cells / pathology
-
Central Nervous System / embryology
-
Central Nervous System / pathology*
-
Core Binding Factor Alpha 2 Subunit
-
Core Binding Factor beta Subunit
-
Crosses, Genetic
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / metabolism
-
Embryo, Mammalian / pathology
-
Gene Dosage
-
Genes, Lethal*
-
Genotype
-
Hematopoiesis / genetics
-
Hemorrhage / genetics
-
In Situ Hybridization
-
Liver / embryology
-
Liver / physiopathology*
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Mice, Mutant Strains
-
Mutagenesis
-
Phenotype
-
Polymerase Chain Reaction
-
Protein Binding
-
Proto-Oncogene Proteins*
-
RNA, Messenger / isolation & purification
-
Stem Cells
-
Transcription Factor AP-2
-
Transcription Factors / genetics*
-
Transcription Factors / metabolism
Substances
-
Cbfb protein, mouse
-
Core Binding Factor Alpha 2 Subunit
-
Core Binding Factor beta Subunit
-
DNA-Binding Proteins
-
Proto-Oncogene Proteins
-
RNA, Messenger
-
Runx1 protein, mouse
-
Transcription Factor AP-2
-
Transcription Factors