The amino acid sequence of ELOVL4 is well conserved evolutionarily from yeast to human.
18 Members of the ELO family are believed to be involved in fatty acid elongation.
37 38 ELOVL4 is expressed in the photoreceptor cells in a number of species.
18 In the mouse the retina, brain, testis, and skin express high amounts of
Elovl4, and these tissues are known to have high requirements for LCFAs in their cellular membranes.
21 Elovl4 expression increases in the retina during the period that photoreceptor outer segments are developing, and a high level of ELOVL4 is maintained throughout life, perhaps because of the requirement for LCFAs in the retina, owing to turnover of photoreceptor outer segment membrane as they undergo repetitive, daily shedding and renewal.
39 Very-long-chain polyunsaturated fatty acids of phosphatidylcholine are synthesized in photoreceptors.
40 Moreover, lower blood levels of DHA and other long-chain fatty acids have been noted in patients with several different genetic forms of photoreceptor degeneration.
41 42 We evaluated but did not find any abnormalities in blood fatty acid composition of the
Elovl4 +/ − mice, despite reduced concentration of several fatty acids in the retina. Although we could discern no obvious pattern in the reduced fatty acids that would place the ELOVL4 enzyme along the fatty acid metabolic pathway in the retina, two LCFAs of 24 carbon atoms were diminished, suggesting that the ELOVL4 protein may be necessary for their synthesis. It was intriguing to note that retinal levels of several shorter fatty acids were also decreased in the
Elovl4 +/ − retinas. LCFAs are broken down and recycled into short-chain nonessential fatty acids, and it is possible that a decrease in long- or very-LCFAs results in lower amounts of short-chain fatty acids. Shortening of the outer segments and photoreceptor loss would reduce the proportion of membrane-rich tissue in the
Elovl4 +/ − retinas relative to the WT and may therefore account for some of the reduced fatty acid content in the
Elovl4 +/ − retinas. However, in such case we would expect the content of DHA, which is the prominent fatty acid in the disc membranes, to be reduced. Because DHA levels were similar in
Elovl4 +/ − and in WT retinas, we suggest that most of the difference in fatty acid content reflects an actual change in fatty acid composition and is not an artifact of different membrane contents in the retinal tissues.