Submitted November 3, 2006
Returned for revision December 18, 2006
Accepted April 11, 2007
Gamete Biology
Sperm Motility Defects and Infertility in Male Mice with a
Mutation in Nsun7, a Member of the Sun Domain-Containing Family of Putative RNA Methyltransferases
Tanya Harris ,
Becky Marquez ,
Susan Suarez ,
and
John Schimenti *
* To whom correspondence should be addressed. E-mail: jcs92{at}cornell.edu.
Abstract
Poor sperm quality is the major cause of infertility in humans. Other than sexlinked factors, the genetic basis for male infertility is poorly defined, largely due to practical difficulties in studying the inheritance of such a trait in humans. As an alternative, we have conducted forward genetic screens in mice to generate relevant models. We report here on the identification and characterization of a chemically-induced mutation, Ste5Jcs1, causing affected male mice to be sterile or subfertile. Mutant sperm exhibited depressed progressive motility, associated with a rigid flagellar midpiece (but not principle piece) segment, which could not be rescued by treatment with agents that stimulate cAMP or calcium signaling pathways. Overall mutant sperm ultrastructure appeared normal, including the axoneme, however the midpiece mitochondrial sheath showed abnormal electron density patterns. Positional cloning of Ste5Jcs1 led to the identification of a mutation in a novel gene called Nsun7, encoding a protein with a Sun domain that is homologous to tRNA and rRNA cytosine methyltransferases. The Ste5Jcs1 mutation therefore uncovers a previously unrecognized biological process in sperm that underscores the functional compartmentalization of the midpiece and principle piece of the flagellum.
Key words:
Gamete Biology •
Testis •
Gametogenesis •
Sperm motility and transport
