Abstract
Despite the increasing interest in other classes of small RNAs, microRNAs (miRNAs) remain the most widely investigated and have been shown to play a role in a number of different processes in mammals. Many studies investigating miRNA function focus on the processing enzyme Dicer1, which is an RNAseIII protein essential for the biogenesis of active miRNAs through its cleavage of precursor RNA molecules. General deletion of Dicer1 in the mouse confirms that miRNAs are essential for development because embryos lacking Dicer1 fail to reach the end of gastrulation. Here we investigate the role of Dicer1 in urogenital tract development. We utilised a conditional allele of the Dicer1 gene and two Cre-expressing lines, driven by HoxB7 and Amhr2, to investigate the effect of Dicer1 deletion on both male and female reproductive tract development. Data presented here highlight an essential role for Dicer1 in the correct morphogenesis and function of the female reproductive tract and confirm recent findings that suggest Dicer1 is required for female fertility. In addition, HoxB7:Cre-mediated deletion in ureteric bud derivatives leads to a spectrum of anomalies in both males and females, including hydronephrotic kidneys and kidney parenchymal cysts. Male reproductive tract development, however, remains largely unaffected in the absence of Dicer1. Thus, Dicer1 is required for development of the female reproductive tract and also normal kidney morphogenesis.
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Acknowledgments
The authors would particularly like to thank Nick Warr, Debora Bogani, Rachel Brixey, and Pam Siggers in the Sexual Development group at MGU, MRC Harwell for advice and support. We thank the staff of the Mary Lyon Centre (MLC) at MRC Harwell for support in animal husbandry, especially Lucie Vizor, Rose Kent, Dan Andrew, and Jackie Harrison. We thank Jim Humphrey, Dave Shipston, and Kate Vowell of the necropsy team of the MLC for assistance with dissections and the histology team for support in sectioning. We are grateful to Kan Pai Chiev for assistance with clinical chemistry. We thank Sue Rodger of the FESA team of the Mammalian Genetics Unit (MGU) for support in rederivation and analysis of preimplantation embryos. We are also grateful to Richard Behringer for supplying Amhr2:Cre mice. Support in statistics was kindly provided by Pete Underhill. Animal procedures used in this study were authorised by UK Home Office Project License PPL 30/2381. ASW acknowledges project grant support from Kidney Research UK and the Wellcome Trust.
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Pastorelli, L.M., Wells, S., Fray, M. et al. Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract. Mamm Genome 20, 140–151 (2009). https://doi.org/10.1007/s00335-008-9169-y
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DOI: https://doi.org/10.1007/s00335-008-9169-y