1. D. M. Maatouk, K. L. Loveland, M. T. McManus, K. Moore and B. D. Harfe (2008) Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79(4): 696-703.
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 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. PMID: [18633141]
2. M. D. Papaioannou, J. L. Pitetti, S. Ro, C. Park, F. Aubry, O. Schaad, C. E. Vejnar, F. Kuhne, P. Descombes, E. M. Zdobnov, M. T. McManus, F. Guillou, B. D. Harfe, W. Yan, B. Jegou and S. Nef (2009) Sertoli cell Dicer is essential for spermatogenesis in mice. Dev Biol 326(1): 250-9.
Abstract Spermatogenesis requires intact, fully competent Sertoli cells. Here, we investigate the functions of Dicer, an RNaseIII endonuclease required for microRNA and small interfering RNA biogenesis, in mouse Sertoli cell function. We show that selective ablation of Dicer in Sertoli cells leads to infertility due to complete absence of spermatozoa and progressive testicular degeneration. The first morphological alterations appear already at postnatal day 5 and correlate with a severe impairment of the prepubertal spermatogenic wave, due to defective Sertoli cell maturation and incapacity to properly support meiosis and spermiogenesis. Importantly, we find several key genes known to be essential for Sertoli cell function to be significantly down-regulated in neonatal testes lacking Dicer in Sertoli cells. Overall, our results reveal novel essential roles played by the Dicer-dependent pathway in mammalian reproductive function, and thus pave the way for new insights into human infertility. PMID: [19071104]
3. G. J. Kim, I. Georg, H. Scherthan, M. Merkenschlager, F. Guillou, G. Scherer and F. Barrionuevo (2010) Dicer is required for Sertoli cell function and survival. Int J Dev Biol 54(5): 867-75.
Abstract Dicer is a key enzyme that processes microRNA precursors into their mature form, enabling them to regulate gene expression. Dicer null mutants die before gastrulation. To study Dicer function in testis development, we crossed mice carrying a conditional Dicer allele with an AMH-Cre transgenic line, thereby inactivating Dicer in Sertoli cells around embryonic day 14.0 (E14.0). Dicer null Sertoli cells show normal embryonic development, and at postnatal day 0 (P0), testis tubules are normal in number and histologically undistinguishable from controls. Subsequently, Dicer-mutant testes show a progressively aberrant development, so that at P6, they contain a reduced number of disorganized testis tubules leading to primary sterility. Apoptosis and prophase I assays reveal a massive wave of apoptosis starting at P3, causing progressive loss of Sertoli cells, but also of germ cells, resulting in drastically reduced testis size. Expression of genes that play crucial roles in testis development, structural integrity and spermatogenesis is downregulated at P0, before morphological changes become apparent, indicating that Dicer-mutant testes are already transcriptionally compromised at this stage. Taken together, the results of this study show that Dicer is required for Sertoli cell function and survival and for spermatogenesis in mice. PMID: [19876815]
Figures for illustrating the function of this protein/gene
Ref: D. M. Maatouk, K. L. Loveland, M. T. McManus, K. Moore and B. D. Harfe (2008) Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79(4): 696-703. PMID: [18633141]
Ref: D. M. Maatouk, K. L. Loveland, M. T. McManus, K. Moore and B. D. Harfe (2008) Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79(4): 696-703. PMID: [18633141]
Ref: D. M. Maatouk, K. L. Loveland, M. T. McManus, K. Moore and B. D. Harfe (2008) Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79(4): 696-703. PMID: [18633141]
Ref: D. M. Maatouk, K. L. Loveland, M. T. McManus, K. Moore and B. D. Harfe (2008) Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79(4): 696-703. PMID: [18633141]