He and his team started this work three years ago looking at heart disease, thinking that Fkbp6 would have a primary role in heart function. "We found no link between this gene and heart disease but we did find that our male mice were unable to breed. When we investigated further, we found that the size of the testes of our mice were massively reduced and that they produced no sperm cells," he recalls.
"Fkbp6 only acts in sperm cells and we found no other defects in our mice besides sex-specific male infertility. While our male mice showed normal sexual behavior and had normal levels of sex hormones, they completely lacked sperm cells. So it's possible that Fkbp6 might be the perfect target for the development of a male birth control pill."
As an additional finding, the researchers say the Fkbp6 gene also seems to play a fundamental role in the normal life of chromosomes in sperm cells. Penninger's group found that Fkbp6 is part of the protein complex that binds maternal and paternal chromosomes in oocytes and sperm cells, a process carried out by meiosis. Meiosis occurs in all sexually reproducing species and allows the genetic exchange between maternal and paternal genomes.
In normal life, each chromosome partners with a chromosome of corresponding structure, position and origin. Penninger and his fellow researchers found that when the Fkbp6 gene was removed from the mice, the chromosomes were unable to identify their correct partners and, instead, paired with non-corresponding chromosomes. Defects in chromosome alignment or genome segregation in germ cells can result in aneuploidies, where subjects carry chromosomes above or below the normal chromosome number. Aneuploidy is a leading cause of spontaneous miscarriages in humans and a trait in many human cancer cells.
Penninger says their research suggests that a protein produced by the Fkbp6 gene is
'"/>
22-May-2003