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Scientists report first transgenic animal developed via retroviral DNA insertion into male germ-line stem cells

PHILADELPHIA Scientists at the University of Pennsylvania School of Veterinary Medicine have successfully used a retrovirus to modify genes in spermatogonial stem cells in a mouse the first instance, in any species, of a transgenic animal created by inserting a gene into male germ-line stem cells.

The inserted gene subsequently appeared in approximately 4.5 percent of offspring of mice transplanted with the altered stem cells, and was transmitted to at least three succeeding generations.

The work is the cover story in the Nov. 6 issue of the Proceedings of the National Academy of Sciences, and will appear tomorrow on the journals web site. The findings should enable the creation of transgenic individuals in a wide range of species, permitting scientists to develop research models for study of numerous human diseases.

Led by Ralph L. Brinster of Penns Department of Animal Biology, the scientists succeeded in inserting a foreign gene in this case the common reporter gene lacZ, whose product is the enzyme -galactosidase into 2 to 20 percent of mouse spermatogonial stem cells in laboratory experiments, a ten-fold improvement over previous attempts.

"These results indicate that there is no intrinsic barrier to the genetic engineering of spermatogonial stem cells using retroviruses, and that once inserted, the foreign genes will continue to be transmitted and expressed from one generation to the next," said Brinster, the Richard King Mellon Professor of Reproductive Physiology at Penn.

All male mammals harbor many spermatogonial stem cells, key repositories of genetic material whose daughter cells give rise after puberty to sperm. In the human male, approximately 1,000 sperm cells, each carrying a different combination of genetic material, are generated in this manner with each heartbeat. Whereas the female germ cell, the egg, stops dividing before birth, male germ-line stem cells continue to divide throughout
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Contact: Steve Bradt
bradt@pobox.upenn.edu
215-573-6604
University of Pennsylvania
22-Oct-2001


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