Fat-1 transgenic mice: a new model for omega-3 research

Abstract

An appropriate animal model that can eliminate confounding factors of diet would be very helpful for evaluation of the health effects of nutrients such as n-3 fatty acids. We recently generated a fat-1 transgenic mouse expressing the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase that converts n-6 to n-3 fatty acids (which is absent in mammals). The fat-1 transgenic mice are capable of producing n-3 fatty acids from the n-6 type, leading to abundant n-3 fatty acids with reduced levels of n-6 fatty acids in their organs and tissues, without the need of a dietary n-3 supply. Feeding an identical diet (high in n-6) to the transgenic and wild-type littermates can produce different fatty acid profiles in these animals. Thus, this model allows well-controlled studies to be performed, without the interference of the potential confounding factors of diet. The transgenic mice are now being used widely and are emerging as a new tool for studying the benefits of n-3 fatty acids and the molecular mechanisms of their action.

Fig. 1

Conversion of n-6 fatty acids (FA) to n-3 fatty acids by an n-3 desaturase that does not exist in mammalian cells. The n-3 desaturase can catalyze introduction of a double bond into n-6 fatty acids at the n-3 position of their hydrocarbon chains to form n-3 fatty acids.

Fig. 2

Partial gas chromatograph traces showing the polyunsaturated fatty acid profiles of total lipids extracted from skeletal muscles of a wild-type mouse (WT, upper panel) and a fat-1 transgenic mouse (TM, lower panel). Both the wild-type and transgenic mice were 8-week-old females and fed on the same diet, which is high in n-6 but low in n-3 fatty acids. Note, the levels of n-6 fatty acids (18:2n-6, 20:4n-6, 22:4n-6 and 22:5n-6) are remarkably lower whereas n-3 fatty acids (marked with *) are abundant in the transgenic muscle (lower panel) compared with the wild type muscle in which there is very little n-3 fatty acids (upper panel).