Endogenous production and elevated levels of long-chain n-3 fatty acids in the milk of transgenic mice.

N-3 Polyunsaturated fatty acids (n-3 PUFA) are important for the normal development and functioning of all organisms. Mammals lack the n-3 fatty acid desaturase required for the synthesis of alpha-linolenic acid (18:3n-3), and are therefore dependent on dietary sources to obtain this essential fatty acid. Currently, the richest source of dietary long-chain n-3 PUFA, eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), are triacylglycerides extracted from rapidly declining marine resources. The nematode Caenorhabditis elegans synthesizes a wide range of PUFA and possesses the only known example of an n-3 fatty acid desaturase enzyme in the animal kingdom. Transgenic mice expressing the C. elegans n-3 desaturase under the control of the lactation-induced goat beta-casein mammary gland promoter were generated via pronuclear microinjection. Significant increases in n-3 PUFA, decreases in n-6 PUFA, and an overall decrease in the n-6:n-3 PUFA ratio were observed in the milk produced by transgenic mice. Neonate mice consuming milk from transgenic females accumulated increased levels of docosahexaenoic acid in their brains. This transgenic model may provide useful information to address some basic questions of neonatal nutrition, and demonstrates one of the steps that would be required to increase the n-3 PUFA content of milk and dairy products endogenously. Increasing the proportion of n-3 PUFA in milk fat would help to improve the nutritional composition of an important component of the North American diet.