
Scientists Develop First
Transgenic Cow Clone for Mastitis Disease ResistanceBy Jan Suszkiw January 10, 2001BELTSVILLE, Md., Jan. 10--U.S. Department of Agriculture and
University of Vermont (UV) researchers have
produced a clone of a pure-bred Jersey cow whose cells may offer a
biotechnological defense against mastitis disease. Geneticist Kevin Wells of USDAs
Agricultural Research Service (ARS) said it will be at least another year
before the cow, named Annie and born in March 2000, begins
producing milk and scientists can begin testing for mastitis resistance. Though
not the first cow clone, Annie is the first to be genetically altered with a
gene for an agricultural application. Mastitis costs U.S. dairy farmers about $1.7 billion annually, including
lost milk revenues, said Wells, with ARS
Gene Evaluation and
Mapping Laboratory at Beltsville. About 30 percent of all mastitis cases in dairy cows are caused by
Staphylococcus aureus bacteria that destroy milk-secreting cells in the
animals mammary gland. But scientists hope that Annie will resist such
cellular attacks by secreting an added protein called lysostaphin. Antibiotics are only effective in about 15 percent of cows infected with
S. aureus, so dairy producers are forced to cull these cows from their
herds. But lysostaphin may offer an alternative defense bioengineered right
into the animals cells. Were also trying to identify naturally occurring resistance
genes, though very few of them have been found, noted Vernon Pursel, the
GEMLs research leader. Whether bioengineered or naturally occurring, he
said, resistance would lessen mastitiss financial drain, and
provide the added public health benefit of reduced antibiotic usage. In 1999 trials with seven transgenic strains of lysostaphin-producing mice,
the protein effectively killed S. aureus bacteria in both the
genetically modified rodents mammary glands and milk, GEML physiologist
Robert Wall said. He and David Kerr of UVs Animal Sciences Department in
Burlington, report the results in January 2001 issue of the journal Nature Biotechnology. S. aureus was targeted by scientists because it is among the most
virulent of mastitis causing pathogens, and causes about 30 percent of all
infections in cows. The gene for lysostaphin--interestingly--comes from a
benign species of Staph--S. simulans--that competes with its virulent
cousins. Large-scale testing of lysostaphin mice in the lab will help researchers
learn whether results observed in these transgenic rodents will apply to Annie
and her offspring. Practical application of the cloning technology is several
years off, however, Pursel said. First, a number of questions must be
thoroughly researched. For example: - How much lysostaphin will be secreted by a transgenic cows mammary
tissues, and will that amount keep Staph at bay?
- How likely are the bacteria to develop lysostaphin resistance?
- And once secreted into milk, whats the proteins biochemical
fate? Is it allergenic, and will it interfere with cheese production or other
processes?
Another objective is to refine the cloning procedure scientists used, called
somatic cell nuclear transfer. Annies start began with a type of somatic
cell called a fibroblast. Using a mild electrical current, scientists inserted
into that fibroblasts nucleus, genes for lysostaphin, a green fluorescent
protein (GFP) tag, and an antibiotic marker. Also inserted was a sheep gene for
beta lactoglobulin, a switch that instructs mammary cells to make
lysostaphin. Later, scientists fused the altered fibroblast to an unfertilized cow egg,
whose nuclear DNA contents had been removed so the fibroblasts could move
in. About 60 percent of fused cells actually survive, and start dividing like a
normal fertilized embryo, said Pursel. The healthiest embryos--which included
Annie--were cultured and implanted into surrogate mothers. So far, Annie is the first calf brought to term. Genetic testing of
umbilical cord tissue at birth confirmed that she is indeed transgenic. Annie
Powell--for whom the Jersey clone is named--Paul Graninger, Neil Talbot, Harold
Hawk, and Linda Mooney are the other ARS contributing team members. Scientific contacts: Kevin Wells or Robert Wall, ARS
Gene Evaluation and
Mapping Laboratory, Beltsville, Md., phone (301) 504-8342, fax (301)
504-8414, [email protected],
[email protected]. U.S. Department of Agriculture |