August 15, 2005Proceedings of the National Academy of Sciences
Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal
Key Points
- To determine the biological role of acetyl-CoA carboxylase 1 (ACC1) in fatty acid metabolism and embryonic development using a targeted gene knockout approach in mice.
- Generated heterozygous (Acc1+/-) and homozygous (Acc1-/-) mutant mice using targeted gene knockout of the Acc1 gene.
- Assessed embryonic survival and developmental morphology through timed matings at embryonic days E7.5, E8.5, and E11.5.
- Quantified tissue mRNA, protein levels, total malonyl-CoA concentrations, and hepatocyte fatty acid synthesis and oxidation rates.
- Heterozygous Acc1+/- mice exhibited normal fertility, body weight, and lifespans, with preserved protein and malonyl-CoA levels despite a 50% reduction in Acc1 mRNA.
- Homozygous Acc1-/- mice suffered complete embryonic lethality, being undeveloped at E7.5, dying by E8.5, and fully resorbed by E11.5.
- Differential phenotypes between viable Acc2-/- and non-viable Acc1-/- mice demonstrate that ACC1 and ACC2 regulate distinct, non-redundant pools of malonyl-CoA.
Authors
Discussion
No takes yet. Share an insight, caveat, or question.
Implication
Gene targeting study demonstrates that acetyl-CoA carboxylase 1 deficiency causes embryonic lethality in mice, indicating distinct metabolic roles for ACC1 and ACC2.
Cite This Study
Abu-Elheiga et al. (2005) studied this question.