TY - JOUR
T1 - Targeted deletion of the murine apobec-1 complementation factor (acf) gene results in embryonic lethality
AU - Blanc, Valerie
AU - Henderson, Jeffrey O.
AU - Newberry, Elizabeth P.
AU - Kennedy, Susan
AU - Luo, Jianyang
AU - Davidson, Nicholas O.
PY - 2005/8
Y1 - 2005/8
N2 - apobec-1 complementation factor (ACF) is an hnRNP family member which functions as the obligate RNA binding subunit of the core enzyme mediating C-to-U editing of the nuclear apolipoprotein B (apoB) transcript. ACF binds to both apoB RNA and apobec-1, the catalytic cytidine deaminase, which then results in site-specific posttranscriptional editing of apoB mRNA. Targeted deletion of apobec1 eliminates C-to-U editing of apoB mRNA but is otherwise well tolerated. However, the functions and potential targets of ACF beyond apoB mRNA editing are unknown. Here we report the results of generating acf knockout mice using homologous recombination. While heterozygous acf-/- mice were apparently healthy and fertile, no viable acf-/- mice were identified. Mutant acf-/- embryos were detectable only until the blastocyst (embryonic day 3.5 [E3.5]) stage. No acf-/- blastocysts were detectable following implantation at E4.5, and isolated acf-/- blastocysts failed to proliferate in vitro. Small interfering RNA knockdown of ACF in either rat (apobec-1-expressing) or human (apobec-1-deficient) hepatoma cells decreased ACF protein expression and induced a commensurate increase in apoptosis. Taken together, these data suggest that ACF plays a crucial role, which is independent of apobec-1 expression, in cell survival, particularly during early embryonic development.
AB - apobec-1 complementation factor (ACF) is an hnRNP family member which functions as the obligate RNA binding subunit of the core enzyme mediating C-to-U editing of the nuclear apolipoprotein B (apoB) transcript. ACF binds to both apoB RNA and apobec-1, the catalytic cytidine deaminase, which then results in site-specific posttranscriptional editing of apoB mRNA. Targeted deletion of apobec1 eliminates C-to-U editing of apoB mRNA but is otherwise well tolerated. However, the functions and potential targets of ACF beyond apoB mRNA editing are unknown. Here we report the results of generating acf knockout mice using homologous recombination. While heterozygous acf-/- mice were apparently healthy and fertile, no viable acf-/- mice were identified. Mutant acf-/- embryos were detectable only until the blastocyst (embryonic day 3.5 [E3.5]) stage. No acf-/- blastocysts were detectable following implantation at E4.5, and isolated acf-/- blastocysts failed to proliferate in vitro. Small interfering RNA knockdown of ACF in either rat (apobec-1-expressing) or human (apobec-1-deficient) hepatoma cells decreased ACF protein expression and induced a commensurate increase in apoptosis. Taken together, these data suggest that ACF plays a crucial role, which is independent of apobec-1 expression, in cell survival, particularly during early embryonic development.
UR - http://www.scopus.com/inward/record.url?scp=23344436132&partnerID=8YFLogxK
U2 - 10.1128/MCB.25.16.7260-7269.2005
DO - 10.1128/MCB.25.16.7260-7269.2005
M3 - Article
C2 - 16055734
AN - SCOPUS:23344436132
SN - 0270-7306
VL - 25
SP - 7260
EP - 7269
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 16
ER -