Dicer1 is required for differentiation of the mouse male germline.
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 approximately 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.
Maatouk
Danielle M
DM
Department of Microbiology and Immunology, University of California San Francisco Diabetes Center, San Francisco, California 94143, USA.
Loveland
Kate L
KL
McManus
Michael T
MT
Moore
Karen
K
Harfe
Brian D
BD
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology*; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D043244:Ribonuclease III; D013081:Sperm Motility / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology
D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases