http://news.bbc.co.uk/low/english/sci/tech/newsid_485000/485123.stm

BBC News Online: Sci/Tech

Monday, October 25, 1999 Published at 23:04 GMT 00:04 UK

Mice 'make human proteins in semen'
By BBC News Online Science Editor Dr David Whitehouse

Scientists have genetically engineered mice to produce human proteins in their semen, which may allow drugs to be farmed from genetically-modified (GM) livestock.

Living organisms are designed to make proteins, and in recent years scientists have harnessed this natural ability to make protein drugs.

One example is using genetically-modified bacteria to produce insulin. Creating animals which produce the proteins in easily-collectable body fluids means a lifetime's supply of the drug.

The mice created by Francois Pothier and colleagues at Laval University, Canada, secrete human growth hormone (hGH) in their ejaculate.

Clearly mice cannot produce significant quantities of this biomaterial, so they suggest that genetically-engineered male pigs, which can produce up to half a litre of semen at a time, could produce pharmaceutical proteins cost-effectively.

To get the mice to secrete hGH, the team used a DNA gene sequence that is only active in male sex glands. They linked this DNA sequence to one which encodes hGH and injected the combined sequence into fertilised mouse eggs.

The result was that the hormone was secreted specifically in the semen of male animals. It was also expressed in the kidney.

The amount of protein in each millilitre of ejaculate was less than in other transgenic systems, such as goats milk, but the scientists think it may be possible to optimise the system to obtain greater quantities.

Experiments are currently under way to test the technique in boars which can produce up to 300 ml, three times a week, indefinitely.

Other work is underway evaluating the use of different bodily fluids as protein factories, in particular using a pig's bladder to produce useful proteins in its urine.

Female sheep and cows have already been modified to include extra genes and produce drugs in their milk.

But this approach has several limitations: the delay before female sexual maturity and the onset of first lactation, and also by the fact that lactation itself only occurs if the animal is pregnant.

If their work gets the go-ahead the researchers say that they could have a herd of 60 pigs producing proteins in just two years. Obtaining a herd of cattle producing the same protein would take at least seven years.

The research is described in Nature Biotechnology.