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(Circulation Research. 2006;98:e66.)
© 2006 American Heart Association, Inc.

Letter to the Editor

Arachidonate 5-Lipoxygenase Variants in Atherosclerosis, Obesity, and Bone Traits

Malcolm A. Lyons

Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Perth, Australia

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

I write regarding publications by Mehrabian et al^1,2 appearing in Circulation Research and a subsequent publication by Kuhn et al³ appearing in Arteriosclerosis, Thrombosis, and Vascular Biology. The key implication from the combination of these reports was that amino acid substitutions in arachidonate 5-lipoxygenase (ALOX5) could account for differences in susceptibility to atherosclerosis between mouse strains CAST/EiJ and C57BL/6J. The two putative amino acid substitutions reported by Mehrabian et al to be present in strain CAST/EiJ¹ were at positions 645 and 646, which are conserved across human, mouse, rat, dog, cow, and chicken. Indeed, when Kuhn et al³ mutated either or both of these residues in the human cDNA, ALOX5 activity was markedly impaired suggesting a key role for one or both of these residues in protein function. Recently, I determined that the coding sequences reported in the first article and implemented in the third article are incorrect.

We detected QTLs for cholesterol traits on Chr 6 in crosses between strains CAST/EiJ and 129S1/SvImJ⁴ and between strains CAST/EiJ and DBA/2J^5,6 that colocalized with Alox5. The coding region of Alox5 was sequenced among these inbred mouse strains. On comparison of all sequences, we made four observations. (1) Our deduced amino acid sequence derived from strain CAST/EiJ (genomic DNA and cDNA) was different to that reported by Mehrabian et al.¹ (2) The amino acid sequence for strain CAST/EiJ was identical to strain C57BL/6J. (3) Residue 645 was identical among all the mouse strains. (4) Strains 129S1/SvImJ and . . . [Full Text of this Article]

This article has been cited by other articles:

				M. Mehrabian Response to Arachidonate 5-Lipoxygenase Variants in Atherosclerosis, Obesity, and Bone Traits Circ. Res., May 12, 2006; 98(9): e68 - e68. [Full Text] [PDF]