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BOR - Papers in Press, published online ahead of print July 16, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.067827
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BIOLOGY OF REPRODUCTION 79, 696–703 (2008)
DOI: 10.1095/biolreprod.108.067827
© 2008 by the Society for the Study of Reproduction, Inc.

Dicer1 Is Required for Differentiation of the Mouse Male Germline1

Danielle M. Maatouk 3 4 5, Kate L. Loveland 6 7, Michael T. McManus 8, Karen Moore 9, and Brian D. Harfe 2 4 5

Department of Microbiology and Immunology,8 University of California San Francisco Diabetes Center, San Francisco, California 94143 Department of Animal Sciences,9 Institute of Food and Agriculture Sciences, University of Florida, Gainesville, Florida 32611 Monash Institute of Medical Research,6 Monash University, Clayton, Victoria 3168, Australia The Australian Research Council Centre of Excellence in Biotechnology and Development,7 Clayton, Victoria 3168, Australia Department of Molecular Genetics and Microbiology4 and the Genetics Institute,5 College of Medicine, University of Florida, Gainesville, Florida 32610

ABSTRACT

MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate gene expression. Hundreds of miRNAs are expressed in mammals; however, their functions are just starting to be uncovered. MicroRNAs are processed from a long hairpin mRNA transcript, down to a ~23-nucleotide duplex. The enzyme Dicer1 is required for miRNA processing, and mouse knockouts of Dicer1 are embryonic lethal before 7.5 days postcoitus. To examine the function of miRNAs specifically in the germline, we used a mouse model that expresses Cre recombinase from the TNAP locus and a floxed Dicer1 conditional allele. Removal of Dicer1 from germ cells resulted in male infertility. Germ cells were present in adult testes, but few tubules contained elongating spermatids. Germ cells that did differentiate to elongating spermatids exhibited abnormal morphology and motility. Rarely, sperm lacking Dicer1 could fertilize wild-type eggs to generate viable offspring. These results show that Dicer1 and miRNAs are essential for proper differentiation of the male germline.

Dicer, microRNA, spermatogenesis, sperm maturation, testis

FOOTNOTES

3Current address: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.

1Supported by the University of Florida startup funds to B.D.H., the National Health and Medical Research Council of Australia Fellowship (384108) to K.L.L., and the Australian Research Council (348239) to K.L.L.

Correspondence: 2FAX: 352 273 8284; e-mail: bharfe{at}mgm.ufl.edu






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Copyright © 2008 by the Society for the Study of Reproduction.