Sperm capture genes to create new life.

Sperm capture genes to create new life

A new kind of biological fusion has taken place in an Italian research lab. Scientists there have discovered that sperm cells can take up foreign DNA molecules, and they report using these sperm to create genetically altered mice. If confirmed, the finding may give researchers a more rapid technique for creating "transgenic" animals that carry foreign genes, says embryologist Jan W. Abramczuk of the National Institute of Dental Research in Bethesda, Md. The research also suggests that the evolutionary process may capitalize on this property of sperm to allow the transfer of genes between species, say the Italian scientists in the June 2 CELL.

"If [the new work] can be reproduced, this will be a very important technique," comments W. French Anderson of the National Heart, Lung, and Blood Institute in Bethesda. At present, the primary method used to create transgenic animals -- which are used in disease research and to improve livestock -- involves microinjecting DNA into embryos. This requires great skill, expensive equipment and a lot of time, Anderson notes.

The finding that sperm cells take up DNA surprised scientists because DNA uptake in other body cells requires harsher chemical conditions than those used in the Italian study. And sperm cells would seem even more impenetrable than other cells in light of their tightly packed genome and the additional membrane the foreign DNA must cross to reach the nucleus, says Jon W. Gordon of Mount Sinai School of Medicine in New York City.

The researchers, led by Corrado Spadafora of the Institute of Biomedical Technology in Rome, incubated mouse sperm with DNA carrying a gene for a bacterial enzyme called chloramphenicol acetyl transferase (CAT). After half an hour, they counted up to 4,000 DNA particles associated with each sperm cell. It is not clear how far the DNA penetrated each sperm or whether it was incorporated into the sperm's genome.

Spadafora and his colleagues then fertilized mouse eggs with DNA-incubated sperm and transferred the eggs to mice serving as surrogate mothers. Screening 250 progeny, the researchers found that about 30 percent carried the foreign DNA -- a success rate slightly above the maximum attained with the microinjection method, they say. They also discovered that mice in the next generation inherited the gene in the expected Mendelian fashion and that certain cells of a sample of transgenic mice contained working CAT enzymes.

Sperm's ability to take up DNA is not unique to mice; the researchers report similar findings using frog and sea urchin sperm. But "the evolutionary importance of this process will remain elusive as long as there is no clear-cut example of a transferred gene that confers a selective advantage to the recipient organism," write Max L. Birnstiel and Meinrad Busslinger of Austria's Research Institute of Molecular Pathology in an accompanying editorial.

Abramczuk says he initially read the Italians' findings with disbelief, noting in particular that the incubation medium contained DNA-degrading enzymes, which should have prevented DNA uptake. He then reproduced the conditions in his own lab and found that the sperm somehow deactivated the enzymes. "As incredible as it may seem, I cannot reject the [Italian researchers'] claim," he says.