nach oben

Pediatric Nephrology

Erschienen in:

01.04.2014 | Review

Wt1 in the kidney—a tale in mouse models

verfasst von: Derya Deniz Ozdemir, Peter Hohenstein

Erschienen in: Pediatric Nephrology | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

Abstract

The WT1 gene was originally identified through its involvement in the development of Wilms tumours. The gene is characterized by a plethora of different isoforms with, in some cases, clearly different functions in transcriptional control and RNA metabolism. Many different mouse models for Wt1 have already been generated, and these are increasingly providing new information on the molecular roles of Wt1 in normal development and disease. In this review we discuss the different models that have been generated and what they have taught us about the role of Wt1 in the kidney.

Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA (1990) Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature 343:774–778PubMedCrossRef

Haber DA, Buckler AJ, Glaser T, Call KM, Pelletier J, Sohn RL, Douglass EC, Housman DE (1990) An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell 61:1257–1269PubMedCrossRef

Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C, Housman DE (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 60:509–520PubMedCrossRef

Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D, Van Heyningen V, Hastie N (1990) The candidate Wilms' tumour gene is involved in genitourinary development. Nature 346:194–197PubMedCrossRef

Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB (1993) The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo. Mech Dev 40:85–97PubMedCrossRef

Miller-Hodges E, Hohenstein P (2012) WT1 in disease: shifting the epithelial-mesenchymal balance. J Pathol 226:229–240PubMedCrossRef

Hohenstein P, Hastie ND (2006) The many facets of the Wilms' tumour gene, WT1. Hum Mol Genet 15(2):R196–R201PubMedCrossRef

Roberts SG (2005) Transcriptional regulation by WT1 in development. Curr Opin Genet Dev 15:542–547PubMedCrossRef

Martinez-Estrada OM, Lettice LA, Essafi A, Guadix JA, Slight J, Velecela V, Hall E, Reichmann J, Devenney PS, Hohenstein P, Hosen N, Hill RE, Munoz-Chapuli R, Hastie ND (2010) Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin. Nat Genet 42:89–93PubMedCentralPubMedCrossRef

10.

Essafi A, Webb A, Berry RL, Slight J, Burn SF, Spraggon L, Velecela V, Martinez-Estrada OM, Wiltshire JH, Roberts SG, Brownstein D, Davies JA, Hastie ND, Hohenstein P (2011) A Wt1-controlled chromatin switching mechanism underpins tissue-specific Wnt4 activation and repression. Dev Cell 21:559–574PubMedCentralPubMedCrossRef

11.

Larsson SH, Charlieu JP, Miyagawa K, Engelkamp D, Rassoulzadegan M, Ross A, Cuzin F, van Heyningen V, Hastie ND (1995) Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. Cell 81:391–401PubMedCrossRef

12.

Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND (1998) WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes. Genes Dev 12:3217–3225PubMedCrossRef

13.

Ladomery M, Sommerville J, Woolner S, Slight J, Hastie N (2003) Expression in Xenopus oocytes shows that WT1 binds transcripts in vivo, with a central role for zinc finger one. J Cell Sci 116:1539–1549PubMedCrossRef

14.

Wells J, Rivera MN, Kim WJ, Starbuck K, Haber DA (2010) The predominant WT1 isoform (+KTS) encodes a DNA-binding protein targeting the planar cell polarity gene Scribble in renal podocytes. Mol Cancer Res 8:975–985PubMedCentralPubMedCrossRef

15.

Niksic M, Slight J, Sanford JR, Caceres JF, Hastie ND (2004) The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum Mol Genet 13:463–471PubMedCrossRef

16.

Vajjhala PR, Macmillan E, Gonda T, Little M (2003) The Wilms' tumour suppressor protein, WT1, undergoes CRM1-independent nucleocytoplasmic shuttling. FEBS Lett 554:143–148PubMedCrossRef

17.

Dudnakova T, Spraggon L, Slight J, Hastie N (2010) Actin: a novel interaction partner of WT1 influencing its cell dynamic properties. Oncogene 29:1085–1092PubMedCrossRef

18.

Moore AW, Schedl A, McInnes L, Doyle M, Hecksher-Sorensen J, Hastie ND (1998) YAC transgenic analysis reveals Wilms' tumour 1 gene activity in the proliferating coelomic epithelium, developing diaphragm and limb. Mech Dev 79:169–184PubMedCrossRef

19.

Costantini F, Kopan R (2010) Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell 18:698–712PubMedCentralPubMedCrossRef

20.

Das A, Tanigawa S, Karner CM, Xin M, Lum L, Chen C, Olson EN, Perantoni AO, Carroll TJ (2013) Stromal-epithelial crosstalk regulates kidney progenitor cell differentiation. Nat Cell Biol 15:1035–1044PubMedCrossRef

21.

Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74:679–691PubMedCrossRef

22.

Wagner KD, Wagner N, Vidal VP, Schley G, Wilhelm D, Schedl A, Englert C, Scholz H (2002) The Wilms' tumor gene Wt1 is required for normal development of the retina. EMBO J 21:1398–1405PubMedCrossRef

23.

Wagner N, Wagner KD, Hammes A, Kirschner KM, Vidal VP, Schedl A, Scholz H (2005) A splice variant of the Wilms' tumour suppressor Wt1 is required for normal development of the olfactory system. Development 132:1327–1336PubMedCrossRef

24.

Herzer U, Crocoll A, Barton D, Howells N, Englert C (1999) The Wilms tumor suppressor gene wt1 is required for development of the spleen. Curr Biol 9:837–840PubMedCrossRef

25.

Koesters R, Ridder R, Kopp-Schneider A, Betts D, Adams V, Niggli F, Briner J, von Knebel DM (1999) Mutational activation of the beta-catenin proto-oncogene is a common event in the development of Wilms' tumors. Cancer Res 59:3880–3882PubMed

26.

Maiti S, Alam R, Amos CI, Huff V (2000) Frequent association of beta-catenin and WT1 mutations in Wilms tumors. Cancer Res 60:6288–6292PubMed

27.

Hastie ND (1994) The genetics of Wilms' tumor—a case of disrupted development. Annu Rev Genet 28:523–558PubMedCrossRef

28.

Stark K, Vainio S, Vassileva G, McMahon AP (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372:679–683PubMedCrossRef

29.

Kispert A, Vainio S, McMahon AP (1998) Wnt-4 is a mesenchymal signal for epithelial transformation of metanephric mesenchyme in the developing kidney. Development 125:4225–4234PubMed

30.

Sim EU, Smith A, Szilagi E, Rae F, Ioannou P, Lindsay MH, Little MH (2002) Wnt-4 regulation by the Wilms' tumour suppressor gene, WT1. Oncogene 21:2948–2960PubMedCrossRef

31.

Davies JA, Ladomery M, Hohenstein P, Michael L, Shafe A, Spraggon L, Hastie N (2004) Development of an siRNA-based method for repressing specific genes in renal organ culture and its use to show that the Wt1 tumour suppressor is required for nephron differentiation. Hum Mol Genet 13:235–246PubMedCrossRef

32.

Hartwig S, Ho J, Pandey P, Macisaac K, Taglienti M, Xiang M, Alterovitz G, Ramoni M, Fraenkel E, Kreidberg JA (2010) Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development. Development 137:1189–1203PubMedCrossRef

33.

Gao F, Maiti S, Alam N, Zhang Z, Deng JM, Behringer RR, Lecureuil C, Guillou F, Huff V (2006) The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci USA 103:11987–11992PubMedCrossRef

34.

Hu Q, Gao F, Tian W, Ruteshouser EC, Wang Y, Lazar A, Stewart J, Strong LC, Behringer RR, Huff V (2011) Wt1 ablation and Igf2 upregulation in mice result in Wilms tumors with elevated ERK1/2 phosphorylation. J Clin Invest 121:174–183PubMedCentralPubMedCrossRef

35.

Bouchard M, Souabni A, Busslinger M (2004) Tissue-specific expression of cre recombinase from the Pax8 locus. Genesis 38:105–109PubMedCrossRef

36.

Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L, Fine RN, Silverman BL, Haber DA, Housman D (1991) Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67:437–447PubMedCrossRef

37.

Gao F, Maiti S, Sun G, Ordonez NG, Udtha M, Deng JM, Behringer RR, Huff V (2004) The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome. Mol Cell Biol 24:9899–9910PubMedCentralPubMedCrossRef

38.

Patek CE, Little MH, Fleming S, Miles C, Charlieu JP, Clarke AR, Miyagawa K, Christie S, Doig J, Harrison DJ, Porteous DJ, Brookes AJ, Hooper ML, Hastie ND (1999) A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome. Proc Natl Acad Sci USA 96:2931–2936PubMedCrossRef

39.

Patek CE, Brownstein DG, Fleming S, Wroe C, Rose L, Webb A, Berry RL, Devenney PS, Walker M, Maddocks OD, Lawrence NJ, Harrison DJ, Wood KM, Miles CG, Hooper ML (2008) Effects on kidney disease, fertility and development in mice inheriting a protein-truncating Denys-Drash syndrome allele (Wt1tmT396). Transgenic Res 17:459–475PubMedCrossRef

40.

Moore AW, McInnes L, Kreidberg J, Hastie ND, Schedl A (1999) YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. Development 126:1845–1857PubMed

41.

Guo JK, Menke AL, Gubler MC, Clarke AR, Harrison D, Hammes A, Hastie ND, Schedl A (2002) WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis. Hum Mol Genet 11:651–659PubMedCrossRef

42.

Menke AL AIJ, Fleming S, Ross A, Medine CN, Patek CE, Spraggon L, Hughes J, Clarke AR, Hastie ND (2003) The wt1-heterozygous mouse; a model to study the development of glomerular sclerosis. J Pathol 200:667–674PubMedCrossRef

43.

Natoli TA, Liu J, Eremina V, Hodgens K, Li C, Hamano Y, Mundel P, Kalluri R, Miner JH, Quaggin SE, Kreidberg JA (2002) A mutant form of the Wilms' tumor suppressor gene WT1 observed in Denys-Drash syndrome interferes with glomerular capillary development. J Am Soc Nephrol 13:2058–2067PubMedCrossRef

44.

Chau YY, Brownstein D, Mjoseng H, Lee WC, Buza-Vidas N, Nerlov C, Jacobsen SE, Perry P, Berry R, Thornburn A, Sexton D, Morton N, Hohenstein P, Freyer E, Samuel K, van't Hof R, Hastie N (2011) Acute multiple organ failure in adult mice deleted for the developmental regulator Wt1. PLoS Genet 7:e1002404PubMedCentralPubMedCrossRef

45.

Royer-Pokora B, Beier M, Henzler M, Alam R, Schumacher V, Weirich A, Huff V (2004) Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. Am J Med Genet A 127A:249–257PubMedCrossRef

46.

Barbaux S, Niaudet P, Gubler MC, Grunfeld JP, Jaubert F, Kuttenn F, Fekete CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K (1997) Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 17:467–470PubMedCrossRef

47.

Hammes A, Guo JK, Lutsch G, Leheste JR, Landrock D, Ziegler U, Gubler MC, Schedl A (2001) Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation. Cell 106:319–329PubMedCrossRef

48.

Natoli TA, McDonald A, Alberta JA, Taglienti ME, Housman DE, Kreidberg JA (2002) A mammal-specific exon of WT1 is not required for development or fertility. Mol Cell Biol 22:4433–4438PubMedCentralPubMedCrossRef

49.

Miles CG, Slight J, Spraggon L, O'Sullivan M, Patek C, Hastie ND (2003) Mice lacking the 68-amino-acid, mammal-specific N-terminal extension of WT1 develop normally and are fertile. Mol Cell Biol 23:2608–2613PubMedCentralPubMedCrossRef

50.

Richard DJ, Schumacher V, Royer-Pokora B, Roberts SG (2001) Par4 is a coactivator for a splice isoform-specific transcriptional activation domain in WT1. Genes Dev 15:328–339PubMedCrossRef

51.

Hosen N, Shirakata T, Nishida S, Yanagihara M, Tsuboi A, Kawakami M, Oji Y, Oka Y, Okabe M, Tan B, Sugiyama H, Weissman IL (2007) The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis. Leukemia 21:1783–1791PubMedCrossRef

52.

Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454:109–113PubMedCentralPubMedCrossRef

53.

Dallosso AR, Hancock AL, Brown KW, Williams AC, Jackson S, Malik K (2004) Genomic imprinting at the WT1 gene involves a novel coding transcript (AWT1) that shows deregulation in Wilms' tumours. Hum Mol Genet 13:405–415PubMedCrossRef

Titel: Wt1 in the kidney—a tale in mouse models
verfasst von: Derya Deniz Ozdemir
Peter Hohenstein
Publikationsdatum: 01.04.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 4/2014
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-013-2673-7

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Wt1 in the kidney—a tale in mouse models

Abstract

Neu im Fachgebiet Pädiatrie

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

Update Pädiatrie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2014

Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation

Controversies on the origin of proliferating epithelial cells after kidney injury

Experimental renal progenitor cells: Repairing and recreating kidneys?

Gene regulatory network of renal primordium development

To bud or not to bud: the RET perspective in CAKUT

Polycystin-1 cleavage and the regulation of transcriptional pathways

Neu im Fachgebiet Pädiatrie

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

Update Pädiatrie