title: Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract.
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.
authors.affiliation: Mammalian Genetics Unit, MRC Harwell, Oxfordshire, OX11 0RD, UK.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Pastorelli
authors.forename: Sara
authors.initials: S
authors.lastname: Wells
authors.forename: Martin
authors.initials: M
authors.lastname: Fray
authors.forename: Adrian
authors.initials: A
authors.lastname: Smith
authors.forename: Tertius
authors.initials: T
authors.lastname: Hough
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Michael T
authors.initials: MT
authors.lastname: McManus
authors.forename: Lee
authors.initials: L
authors.lastname: Smith
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Woolf
authors.forename: Michael
authors.initials: M
authors.lastname: Cheeseman
authors.forename: Andy
authors.initials: A
authors.lastname: Greenfield
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D047108:Embryonic Development; D004722:Endoribonucleases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005298:Fertility; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043244:Ribonuclease III; D013045:Species Specificity; D014566:Urogenital System / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development*
chemical_list: D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases