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Molecular and Cellular Biology, August 2005, p. 7260-7269, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.7260-7269.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Targeted Deletion of the Murine apobec-1 Complementation Factor (acf) Gene Results in Embryonic Lethality

Valerie Blanc,1 Jeffrey O. Henderson,1 Elizabeth P. Newberry,1 Susan Kennedy,1 Jianyang Luo,1 and Nicholas O. Davidson1,2*

Division of Gastroenterology, Department of Medicine,1 Pharmacology and Molecular Biology, Washington University School of Medicine, St. Louis, Missouri 631102

Received 15 December 2004/ Returned for modification 24 February 2005/ Accepted 17 May 2005

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.

* Corresponding author. Mailing address: Washington University School of Medicine, Division of Gastroenterology, Box 8124, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 326-2027. Fax: (314) 362-2033. E-mail: nod{at}wustl.edu.

Molecular and Cellular Biology, August 2005, p. 7260-7269, Vol. 25, No. 16
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.16.7260-7269.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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