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This Article Full Text Full Text (PDF) [Supplemental Data] All Versions of this Article: 77/2/376    most recent biolreprod.106.058669v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Harris, T. Articles by Schimenti, J. Search for Related Content PubMed PubMed Citation Articles by Harris, T. Articles by Schimenti, J. Agricola Articles by Harris, T. Articles by Schimenti, J.

Sperm Motility Defects and Infertility in Male Mice with a Mutation in Nsun7, a Member of the Sun Domain-Containing Family of Putative RNA Methyltransferases¹

Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853

ABSTRACT

Poor sperm quality is the major cause of infertility in humans. Other than sex-linked factors, the genetic basis for male infertility is poorly defined, largely due to practical difficulties in studying the inheritance of this trait in humans. As an alternative, we have conducted forward genetic screens in mice to generate relevant models. We report on the identification and characterization of a chemically-induced mutation, Ste5Jcs1, which causes affected male mice to be sterile or subfertile. Mutant sperm exhibited depressed progressive motility associated with a rigid flagellar midpiece (but not principal 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, although 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, which encodes a protein with a Sun domain that is homologous to tRNA and rRNA cytosine methyltransferases. Therefore, Ste5Jcs1 mutation uncovers a previously unrecognized biological process in sperm that underscores the functional compartmentalization of the midpiece and principal piece of the flagellum.

gamete biology,, gametogenesis,, mitochondria,, mouse,, mutagenesis,, sperm midpiece,, sperm motility and transport,, spermiogenesis,, testis

¹Supported by a grant (HD 35984) from the National Institute of Child Health and Human Development to J.S., and by a grant (MCB-0421855) from the National Science Foundation to S.S.

Correspondence: ²FAX: 607 253 3789; e-mail: jcs92{at}cornell.edu