ANIMAL RESEARCH NEWS

HOPE FOR SUFFERERS OF LACTOSE INTOLERANCE

The development of transgenic livestock with genetically modified milk has been driven by two major goals. One goal is the production of valuable pharmaceutical proteins as an added component in milk. The second goal is the alteration of milk components themselves to improve milk's nutritional quality. These new products with enhanced food value have been termed nutraceuticals.

Milk is a high quality food source. It is rich in carbohydrate, protein, and fat, as well as vitamins, minerals, and growth factors. Lactose is the major carbohydrate source in milk and also serves to regulate the water content of milk during production.

Lactose is normally hydrolyzed by the intestinal enzyme lactase-phlorizin hydrolase into galactose and glucose. However, about 70% of adults lack sufficient lactase and suffer from lactose intolerance, an intestinal disorder that arises when milk or milk products are consumed. In these people, lactose remains unabsorbed in the intestinal tract and causes severe intestinal distress. The symptoms include abdominal pain and diarrhoea, which can lead to severe dehydration.

In most cases of lactose intolerance, lactase levels naturally decline after weaning, particularly in certain ethnic groups such as Orientals, Arabs, Jews, Africans, Indians, and Mediterraneans. However, lactase activity can also be lost due to disease and is considered a normal part of aging.

Because of the nutritional value of milk and its widespread use in many food products, low lactose milk would be of significant benefit to a large percentage of the adult population. Post-harvest treatment of milk with microbial lactose hydrolyzing enzymes can produce low-lactose milk but such treatment increases the cost prohibitively. Thus, transgenic dairy cattle capable of producing low-lactose milk would be advantageous as a low cost alternative.

In the February 1999 issue of Nature Biotechnology, French researchers reported an important proof of concept study. They developed transgenic mice that expressed intestinal lactase in the mammary gland and produced low-lactose milk. A DNA construct containing the rat intestinal lactase-phlorizin hydrolase cDNA under the control of the mammary specific alpha lactalbumin promoter was introduced into mice. Transgenic mice expressed the foreign lactase construct during lactation and secreted lactase into milk.

Lactase synthesis caused a 50-85% reduction in milk lactose and a concomitant increase in glucose and galactose content. Milk collected immediately after suckling showed a 50% decline in lactose, whereas milk collected 8 hours after suckling showed an 85% reduction. These results indicate that the lactase secreted into the milk is active and that enzymatic hydrolysis of the lactose in milk occurs during storage in the mammary gland.

The nutritional quality of milk from these transgenic mice was not significantly altered. There was no obvious change in fat, protein, or mineral content. In addition, newborn mice suckling low-lactose milk from transgenic mice exhibited a similar growth curve compared with mice suckling milk from nontransgenic control mice.

Previous attempts to reduce the lactose content in mouse milk have involved the development of transgenic mice lacking the alpha lactalbumin gene. Milk from these transgenic mice contains no lactose. Because lactose is essential for maintaining the proper fluidity of milk, the absence of lactose results in highly viscous milk.

Source

Jost B, Vilotte J-L, Duluc I, Rodeau J-L, and Freund J-N. 1999.
Production of low-lactose milk by ectopic expression of intestinal lactase in the mouse mammary gland. Nature Biotechnology 17:160-164.