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5-Animals: ISBNews_99.03/Lactose_free_milk

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ressource: 
ISB NEWS REPORT, March 1999


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                       ANIMAL RESEARCH NEWS
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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 milkAEs 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 diarrhea, 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. 

The current mouse studies offer hope for the many individuals who suffer 
from
lactose intolerance. Medical studies have shown that a 50-70% decrease in
lactose is sufficient to prevent intestinal disorders in 
lactose-intolerant
individuals.
Someday dairy products, like ice cream, may be available to everyone as a
source of pleasure without the pain. 

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. 

Eric Wong 
Department of Animal and Poultry Sciences 
Virginia Tech 
ewong@vt.edu 

__________________________
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Systems
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Polytechnic Institute and State University. It does not necessarily 
reflect the
views of the U.S. Department of Agriculture or of Virginia Tech. The News
Report may be freely photocopied or otherwise distributed without charge. 

     Patricia L. Traynor, Editor (traynor@vt.edu) 
     Ruth Irwin, Associate Editor (rirwin@nbiap.biochem.vt.edu) 

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