Originally created 05/30/97

Report: Large stretches of human DNA planted in mice



NEW YORK (AP) - Scientists have managed to insert large chunks of human DNA in mice, an astonishing breakthrough that will allow a new generation of research into genes, birth defects and genetic diseases.

Researchers have put human DNA into mice for years, but not on this scale. Some of the newly developed mice have a complete human chromosome - one of the rod-like structures that hold genes - containing some 50 times the amount of DNA scientists had been able to transfer before.

Not only did the transplanted genes work normally, but some of the mice were also able to pass the chunks of DNA they got onto their offspring.

Nearly all the mice looked normal, though some males had small testes and were sterile.

The results are "incredible," said Alcino Silva, a mouse genetics researcher at the Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y.

Scientists didn't think that chromosome-size chunks of DNA from one mammal could settle in permanently in a different mammal and function normally, he said.

And "it's amazing that such large fragments of DNA can be passed on to their offspring," Silva said.

"This is a quite important research breakthrough," said gene expert Huntington Willard of the Case Western Reserve University School of Medicine and University Hospitals of Cleveland.

The work is reported in the June issue of the journal Nature Genetics by scientists at the Central Laboratories for Key Technology at the Kirin Brewery Co. in Yokahama, Japan, and elsewhere in Japan.

Even Isao Ishida, one of the study authors at Kirin, said he was surprised it worked.

He and colleagues made hybrid mouse-human cells that contained single human chromosomes or chunks of chromosomes. Then they fused these cells to embryonic mouse cells, and put these cells into early mouse embryos. The embryos were then put into mice to grow into newborns.

Some of the resulting mice contained the human chromosome 22 in many of their cells. And mice that had gotten a fragment of human chromosome 2 were able to pass it on to some of their offspring.

Ishida said scientists wanted to create mice that make human versions of blood proteins called antibodies. The proteins could be useful in medicine.

But Silva and Willard said the implications of the work go far beyond that, to allowing new kinds of studies of how genes work normally and in disease. That research that might eventually turn into new medical treatments.

Genes act like members of a neighborhood on their chromosomes, responding to other genes that can be a good distance away. The new work means entire genetic neighborhoods can be transplanted into mice, so scientists can study what turns particular genes on and off, Willard said.

Since the mice carry the transplanted DNA from well before birth, they could help scientists learn about how genes work in early human development. That could shed light on birth defects.

In addition, large-scale transplants will enable scientists to reproduce human diseases that occur when parts of chromosomes are duplicated, Silva said.

The Japanese scientists said they are already developing mice with a human chromosome 21 to investigate Down syndrome, which is caused by having an extra copy of that chromosome.

In the past, human DNA put into mice has attached itself to a mouse chromosome. But in the Japanese work, the transplanted DNA stayed apart. Silva said that's an advantage, because it might allow scientists to transplant even bigger chunks.