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Acyl‐CoA Binding Protein Gene Ablation Induces Pre‐implantation Embryonic Lethality in Mice
Author(s) -
Landrock Danilo,
Atshaves Barbara P.,
McIntosh Avery L.,
Landrock Kerstin K.,
Schroeder Friedhelm,
Kier Ann B.
Publication year - 2010
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-010-3437-9
Subject(s) - biology , embryo , embryonic stem cell , embryogenesis , binding protein , microbiology and biotechnology , zygote , downregulation and upregulation , null allele , blastocyst , gene , biochemistry , phenotype
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.