PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
 
Mol Cell Biol. 1991 March; 11(3): 1707–1712.
PMCID: PMC369476

Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development.

Abstract

The human Wilms' tumor predisposition gene, WT1, is a Cys-His zinc finger polypeptide which appears to be a transcription factor controlling gene expression during embryonic kidney development. In order to analyze the role of the WT1 gene in nephroblast differentiation, we have isolated the murine homolog of human WT1. An extremely high level of amino acid sequence conservation (greater than 95%) extends throughout all regions of the predicted mouse and human WT1 polypeptides. Two alternative splices within the WT1 transcript have been conserved between mice and humans, suggesting that these have functional significance. Expression of the mouse WT1 mRNA in fetal kidney increases during late gestation, peaks just prior to or shortly after birth, and declines dramatically by 15 days postpartum. Developmental regulation of WT1 expression appears to be selective for the kidney. The restriction of WT1 expression to a limited number of tissues is in contrast to previously described tumor suppressor genes. In addition, the narrow window of time during which WT1 is expressed at high levels in the kidney is consistent with the origin of Wilms' tumor from primitive nephroblasts and the postulated role of this gene as a negative regulator of growth.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Auffray C, Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. [PubMed]
  • Avner P, Amar L, Dandolo L, Guénet JL. Genetic analysis of the mouse using interspecific crosses. Trends Genet. 1988 Jan;4(1):18–23. [PubMed]
  • Bernards R, Shackleford GM, Schackleford GM, Gerber MR, Horowitz JM, Friend SH, Schartl M, Bogenmann E, Rapaport JM, McGee T, et al. Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6474–6478. [PubMed]
  • Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. [PubMed]
  • DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huang CM, Lee WH, Marsilio E, Paucha E, Livingston DM. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988 Jul 15;54(2):275–283. [PubMed]
  • Dyson N, Howley PM, Münger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989 Feb 17;243(4893):934–937. [PubMed]
  • Feinberg AP, Vogelstein B. Hypomethylation of ras oncogenes in primary human cancers. Biochem Biophys Res Commun. 1983 Feb 28;111(1):47–54. [PubMed]
  • Francke U, Holmes LB, Atkins L, Riccardi VM. Aniridia-Wilms' tumor association: evidence for specific deletion of 11p13. Cytogenet Cell Genet. 1979;24(3):185–192. [PubMed]
  • Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. [PubMed]
  • Friend SH, Horowitz JM, Gerber MR, Wang XF, Bogenmann E, Li FP, Weinberg RA. Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9059–9063. [PubMed]
  • Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature. 1990 Feb 22;343(6260):774–778. [PubMed]
  • Glaser T, Lane J, Housman D. A mouse model of the aniridia-Wilms tumor deletion syndrome. Science. 1990 Nov 9;250(4982):823–827. [PubMed]
  • Gross-Bellard M, Oudet P, Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. [PubMed]
  • Haber DA, Buckler AJ, Glaser T, Call KM, Pelletier J, Sohn RL, Douglass EC, Housman DE. An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell. 1990 Jun 29;61(7):1257–1269. [PubMed]
  • Henry I, Grandjouan S, Couillin P, Barichard F, Huerre-Jeanpierre C, Glaser T, Philip T, Lenoir G, Chaussain JL, Junien C. Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma. Proc Natl Acad Sci U S A. 1989 May;86(9):3247–3251. [PubMed]
  • Knudson AG., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. [PubMed]
  • Knudson AG, Jr, Strong LC. Mutation and cancer: a model for Wilms' tumor of the kidney. J Natl Cancer Inst. 1972 Feb;48(2):313–324. [PubMed]
  • Koufos A, Grundy P, Morgan K, Aleck KA, Hadro T, Lampkin BC, Kalbakji A, Cavenee WK. Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. Am J Hum Genet. 1989 May;44(5):711–719. [PubMed]
  • Lewis WH, Yeger H, Bonetta L, Chan HS, Kang J, Junien C, Cowell J, Jones C, Dafoe LA. Homozygous deletion of a DNA marker from chromosome 11p13 in sporadic Wilms tumor. Genomics. 1988 Jul;3(1):25–31. [PubMed]
  • Matsunaga E. Genetics of Wilms' tumor. Hum Genet. 1981;57(3):231–246. [PubMed]
  • Meyers DA, Beaty TH, Maestri NE, Kittur SD, Antonarakis SE, Kazazian HH., Jr Multipoint mapping studies of six loci on chromosome 11. Hum Hered. 1987;37(2):94–101. [PubMed]
  • MILLER RW, FRAUMENI JF, Jr, MANNING MD. ASSOCIATION OF WILMS'S TUMOR WITH ANIRIDIA, HEMIHYPERTROPHY AND OTHER CONGENITAL MALFORMATIONS. N Engl J Med. 1964 Apr 30;270:922–927. [PubMed]
  • Nisen PD, Zimmerman KA, Cotter SV, Gilbert F, Alt FW. Enhanced expression of the N-myc gene in Wilms' tumors. Cancer Res. 1986 Dec;46(12 Pt 1):6217–6222. [PubMed]
  • Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D, et al. The candidate Wilms' tumour gene is involved in genitourinary development. Nature. 1990 Jul 12;346(6280):194–197. [PubMed]
  • Reeve AE, Sih SA, Raizis AM, Feinberg AP. Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells. Mol Cell Biol. 1989 Apr;9(4):1799–1803. [PMC free article] [PubMed]
  • Riccardi VM, Sujansky E, Smith AC, Francke U. Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion. Pediatrics. 1978 Apr;61(4):604–610. [PubMed]
  • Robert B, Barton P, Minty A, Daubas P, Weydert A, Bonhomme F, Catalan J, Chazottes D, Guénet JL, Buckingham M. Investigation of genetic linkage between myosin and actin genes using an interspecific mouse back-cross. Nature. 1985 Mar 14;314(6007):181–183. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Semsei I, Ma SY, Cutler RG. Tissue and age specific expression of the myc proto-oncogene family throughout the life span of the C57BL/6J mouse strain. Oncogene. 1989 Apr;4(4):465–471. [PubMed]
  • Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990 Apr 6;248(4951):76–79. [PubMed]
  • Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA, Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature. 1988 Jul 14;334(6178):124–129. [PubMed]
  • Zimmerman KA, Yancopoulos GD, Collum RG, Smith RK, Kohl NE, Denis KA, Nau MM, Witte ON, Toran-Allerand D, Gee CE, et al. Differential expression of myc family genes during murine development. Nature. 319(6056):780–783. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)