Acyl‐CoA Binding Protein Gene Ablation Induces Pre‐implantation Embryonic Lethality in Mice

Abstract

Unique among the intracellular lipid binding proteins, acyl-CoA binding protein (ACBP) exclusively binds long-chain fatty acyl-CoAs (LCFA-CoAs). To test if ACBP is an essential protein in mammals, the ACBP gene was ablated by homologous recombination in mice. While ACBP heterozygotes appeared phenotypically normal, intercrossing of the heterozygotes did not produce any live homozygous deficient (null) ACBP (−/−) pups. Heterozygous and wild type embryos were detected at all post-implantation stages, but no homozygous ACBP-null embryos were obtained-suggesting that an embryonic lethality occurred at a pre-implantation stage of development, or that embryos never formed. While ACBP-null embryos were not detected at any blastocyst stage, ACBP-null embryos were detected at the morula (8-cell), cleavage (2-cell), and zygote (1-cell) pre-implantation stages. Two other LCFA-CoA binding proteins, sterol carrier protein-2 (SCP-2) and sterol carrier protein-x (SCP-x) were significantly upregulated at these stages. These findings demonstrate for the first time that ACBP is an essential protein required for embryonic development and its loss of function may be initially compensated by concomitant upregulation of two other LCFA-CoA binding proteins, but only at the earliest pre-implantation stages. The fact that ACBP is the first known intracellular lipid binding protein whose deletion results in embryonic lethality suggests its vital importance in mammals.

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

“…However, the precise role of this protein in mammalian physiology remains elusive. Knock-out of the Acbp gene in mice has recently been reported to be embryonically lethal (33). This contradicts our findings and the report by Lee et al (32), which show that mice depleted of ACBP are viable.…”

“…Furthermore, lipid analyses showed that they have a decreased amount of TAG on the fur compared with control mice, whereas TAG levels in the skin and liver were similar. While this paper was in preparation, a new report was published showing that disruption of ACBP in mice causes preimplantation embryonic lethality (33). The molecular basis for these findings, which are at odds with results from our laboratory and those from the nm1054 mice, is not clear.…”

The acyl-CoA binding protein is required for normal epidermal barrier function in mice

“…We have shown that the mice suffer from a delayed adaptation of the liver to weaning due to a delayed induction of lipogenic pathways. In contrast to our data, Kier and colleagues reported that targeted disruption of ACBP leads to embryonic preimplantation lethality ( 25 ). The reason for this is unclear, but it may be caused by differences in targeting strategies.…”

Plant acyl-CoA-binding proteins: An emerging family involved in plant development and stress responses

“…Interestingly, studies on mice ACBPs had revealed that depletion of either the 10-kDa ACBP or ACDB3 (consisting of an ACB domain and a phosphotyrosine-binding domain) resulted in embryonic lethality [151,152].…”