Response to Arachidonate 5-Lipoxygenase Variants in Atherosclerosis, Obesity, and Bone Traits
Since learning of the Letter to the Editor by Lyons1 we sequenced the 5-lipoxygenase (5-LO) gene in strains 129/SvJ, CAST/EiJ, and a congenic strain carrying a CAST/Ei allele. The sequences are in agreement with those indicated by Dr Lyons. CAST is a “wild-derived” strain, and we can only speculate that the stock we sequenced may not have been fully inbred; we obtained our stocks in or around 1990 from the Jackson Laboratory. When we reported the 5-LO amino acid differences between CAST and B6, we were unaware of their effect on enzymatic activity that was subsequently reported by Kuhn et al.2
Because we based our conclusions in our article solely on the low transcript and protein levels observed in congenic mice carrying the CAST 5-LO allele, the validity of our results are not altered. Overall, our studies in mice and humans as well as more recent ones from other groups are consistent with the proatherogenic role that 5-LO and the leukotriene pathway play in cardiovascular disease.
Lyons MA. Arachidonate 5-lipoxygenase variants in atherosclerosis, obesity, and bone traits. Circ Res. 2006; 98: e66–e66.
Kuhn H, Anton M, Gerth C, Habenicht A. Amino acid differences in the deduced 5-lipoxygenase sequence of CAST atherosclerosis-resistance mice confer impaired activity when introduced into the human ortholog. Arterioscler Thromb Vasc Biol. 2003; 23: 1072–1076.