Back in the 70s, researchers were able to position the luxoid mutation on mouse chromosome 9. Using modern methods and the published mouse genome sequence, UW researchers were able to identify the mutation at a gene called ZFP145, which produces the protein PLZF. Using a fluorescent antibody against the PLZF protein, the researchers were able to show directly that PLZF is expressed in the adult germ stem cells. The researchers went on to show that another protein, OCT4, which functions to maintain the stem cells in the early embryo and in cultured embryonic stem cells, is also present in the adult germ stem cell. This important finding confirms earlier published studies suggesting that the adult germ stem cells are not far removed from embryonic stem cells.

Identification of the mutation may have significant effects for both infertility and contraception research. In terms of infertility, researchers may someday find a link between the gene and a gradual loss of germ cells within the human testes, Braun said. It ™s possible that the mutation may tip the infertile man ™s stem cells toward differentiation: their stem cells produce sperm for a while, and then are depleted and become infertile “ as happens in the luxoid mice. In theory, that and other discoveries might be used to fashion a therapy to rescue human germ cells and maintain sperm production.

In the same way, any practical implications for contraceptive research are many years away, Braun said: "Luxoid appears to be important in the cells ™ decision whether to remain a stem cell, or differentiate. If we can understand all the players then maybe we could develop a drug that could block the decision to become sperm “ a contraceptive that would be reversible." However, Braun stressed that such products are many, many years away and will require considerable research.

Researchers also hope to someday be able to reverse the developmental process and create embryonic stem cells from adult germ stem cells. Embryonic stem cells are "more pluripotent" than adult stem cells. The embryonic stem cells could then be used in transplantation therapy in patients with degenerative diseases of other tissues. depts.washington/hsnews/