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forwarded by Henning Strodthoff, GeN
ISB NEWS REPORT, March 1999
ANIMAL RESEARCH NEWS
HOPE FOR SUFFERERS OF LACTOSE INTOLERANCE
The development of transgenic livestock with genetically modified milk
driven by two major goals. One goal is the production of valuable
pharmaceutical proteins as an added component in milk. The second goal is
alteration of milk components themselves to improve milkAEs nutritional
These new products with enhanced food value have been termed
Milk is a high quality food source. It is rich in carbohydrate, protein,
well as vitamins, minerals, and growth factors. Lactose is the major
carbohydrate source in milk and also serves to regulate the water content
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
arises when milk or milk products are consumed. In these people, lactose
remains unabsorbed in the intestinal tract and causes severe intestinal
The symptoms include abdominal pain and diarrhea, which can lead to severe
In most cases of lactose intolerance, lactase levels naturally decline
weaning, particularly in certain ethnic groups such as Orientals, Arabs,
Africans, Indians, and Mediterraneans. However, lactase activity can also
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
products, low lactose milk would be of significant benefit to a large
of the adult population. Post-harvest treatment of milk with microbial
hydrolyzing enzymes can produce low-lactose milk but such treatment
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
that expressed intestinal lactase in the mammary gland and produced
milk. A DNA construct containing the rat intestinal lactase-phlorizin
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
increase in glucose and galactose content. Milk collected immediately
suckling showed a 50% decline in lactose, whereas milk collected 8 hours
suckling showed an 85% reduction. These results indicate that the lactase
secreted into the milk is active and that enzymatic hydrolysis of the
milk occurs during storage in the mammary gland.
The nutritional quality of milk from these transgenic mice was not
altered. There was no obvious change in fat, protein, or mineral content.
addition, newborn mice suckling low-lactose milk from transgenic mice
a similar growth curve compared with mice suckling milk from nontransgenic
Previous attempts to reduce the lactose content in mouse milk have
development of transgenic mice lacking the alpha lactalbumin gene. Milk
these transgenic mice contains no lactose. Because lactose is essential
maintaining the proper fluidity of milk, the absence of lactose results in
The current mouse studies offer hope for the many individuals who suffer
lactose intolerance. Medical studies have shown that a 50-70% decrease in
lactose is sufficient to prevent intestinal disorders in
Someday dairy products, like ice cream, may be available to everyone as a
source of pleasure without the pain.
Jost B, Vilotte J-L, Duluc I, Rodeau J-L, and Freund J-N. 1999.
low-lactose milk by ectopic expression of intestinal lactase in the mouse
mammary gland. Nature Biotechnology 17:160-164.
Department of Animal and Poultry Sciences
ISB News Report
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