A team of researchers from the University of Pennsylvania School of Veterinary Medicine has characterized a protein responsible for sperm tail formation that, when missing, causes male infertility, brain abnormalities and other problems in mice.
Jeremy Wang , an associate professor of developmental biology and director of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet, led the study, collaborating with postdoctoral researcher Jian Zhou and research specialists Fang Yang and Adrian Leu.
The work, published in the journal PLoS Genetics, has implications for providing genetic counseling and in vitro fertilization to men with certain infertility problems, as well as to the one in 16,000 people who suffer from a condition known as Kartagener Syndrome, or primary ciliary dyskinesia.
Some men with infertility have sperm that cannot swim properly. One of the causes of this immobility may be a disruption in the function of cilia, hair-like structures that helps cells move themselves or other objects around. The root cause of primary ciliary dyskinesia, or PCD, also appears to be a defect in cilia function.
Delving into the complex structure of cilia, the Penn researchers examined a protein called MNS1 or meiosis-specific nuclear structural protein 1, which they found located in the sperm tail.
To get at the function of MNS1, the team created mice bred to lack the protein. Though the mutant mice grew normally, fewer were born than expected, indicating that the mutation might be lethal in some embryos or very young mice.
In addition, Wang said, "the mutation has a very interesting phenotype."
Male mice that lacked MNS1 were sterile. Their sperm count was only 8 percent of that seen in normal mice, and the vast majority of sperm present had very short tails, impairing their ability to swim. The fact that the sperm had normal heads but malformed tails also indicated to the scientist that the MNS1 mutation affected formation of the sperm tail, which is a specialized type of cilium.