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Gene Review

ur  -  urogenital

Mus musculus

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Disease relevance of ur


High impact information on ur

  • Almost 1% of human infants are born with urogenital abnormalities, many of which are linked to irregular connections between the distal ureters and the bladder [2].
  • During embryogenesis, Sox9 is expressed in all cartilage primordia and cartilages, coincident with the expression of the collagen alpha1(II) gene (Col2a1) . Sox9 is also expressed in other tissues, including the central nervous and urogenital systems [6].
  • The Wilms' tumour suppressor gene 1 (WT1) (1,2) encodes four C2H2 zinc finger-containing proteins (3) critical for normal mammalian urogenital development (4) [7].
  • The linear transcript was not detected in any other fetal tissue nor in any adult tissue tested, and was expressed only in the genital ridge portion of the urogenital ridge [8].
  • In humans, germline mutations of the WT-1 tumor suppressor gene are associated with both Wilms' tumors and urogenital malformations [9].

Chemical compound and disease context of ur


Biological context of ur


Anatomical context of ur


Associations of ur with chemical compounds

  • Immunohistochemistry analysis of murine prostate development demonstrated epithelial expression of CSF-1R during the protrusion of prostatic buds from the urogenital sinus, during the prepubertal and androgen-driven proliferative expansion and branching of the gland, with a decline in older animals [24].
  • Adenosis occurred in transplanted C57BL and BALB/c mice Müllerian-derived reproductive tract regions, cervix, and/or fornix (FX), and middle vagina but never in the urogenital sinus-derived portion of the vagina, after a 1-mo exposure to endogenous ovarian hormones or exogenous estradiol (E2) [25].
  • BPH-1 cells were induced to form tumors either by recombination with human prostatic carcinoma-associated fibroblasts (CAFs) or by exposure to carcinogenic doses of testosterone and estradiol (T+E2) after recombination with rat urogenital sinus mesenchyme [26].
  • Of the urogenital tumors induced by arsenic plus diethylstilbestrol, 80% were malignant, and 55% were multiple site [27].
  • As such, the tumor line will serve as a useful model for studying sex steroid-responsive cells of the urogenital epithelium [28].

Physical interactions of ur


Regulatory relationships of ur

  • BMP7 is expressed in the periurethral urogenital mesenchyme prior to formation of the prostate buds and, subsequently, in the prostate epithelium [30].
  • At later stages, Lbx2 transcripts are expressed in the brain and organs derived from the urogenital ridge, including the gonadal tubercle, kidneys, and adrenal glands [31].
  • At the onset of ductal morphogenesis in the developing prostate, Shh expression condenses at evaginations of urogenital sinus epithelium and activates Gli transcription factors in the adjacent mesenchyme [32].
  • At the same time, Emx2 is expressed in the epithelial components of the developing urogenital system and, in Emx2 mutant mice, the kidneys, ureters, gonads and genital tracts were completely missing [33].
  • The Bmp4 gene was most highly expressed in the male urogenital sinus from embryonic day 14 through birth, a period marked by formation of main prostatic ducts and initiation of ductal branching [34].

Other interactions of ur

  • Here we show that transcripts of the LIM homeobox gene Lhx9 are present in urogenital ridges of mice at embryonic day 9.5; later they localize to the interstitial region as morphological differentiation occurs [19].
  • The gonads of Pod1 knockout (KO) mice were markedly hypoplastic, and the urogenital tracts of both XX and XY mice remained indistinguishable throughout embryogenesis [35].
  • PPARgamma and PBP expression overlapped in the brown fat and urogenital sinus at stage E15.5 of embryogenesis, whereas SRC-1 expression occurred mostly in neuroepithelium and cartilage between stages E9.5 and E13.5 of embryogenesis [36].
  • Nonetheless, the chemical inhibitor of Shh signaling, cyclopamine, produced a graded inhibition of Gli gene expression (Gli1>Gli2>Gli3) in urogenital sinus explants that was paralleled by a severe inhibition of ductal budding [37].
  • The addition of Gdnf protein to urogenital tracts taken from Gdf11 null embryos induced ectopic ureteric bud formation along the Wolffian duct [38].

Analytical, diagnostic and therapeutic context of ur


  1. Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. Larsson, S.H., Charlieu, J.P., Miyagawa, K., Engelkamp, D., Rassoulzadegan, M., Ross, A., Cuzin, F., van Heyningen, V., Hastie, N.D. Cell (1995) [Pubmed]
  2. Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Batourina, E., Choi, C., Paragas, N., Bello, N., Hensle, T., Costantini, F.D., Schuchardt, A., Bacallao, R.L., Mendelsohn, C.L. Nat. Genet. (2002) [Pubmed]
  3. Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development. Niederreither, K., Abu-Abed, S., Schuhbaur, B., Petkovich, M., Chambon, P., Dollé, P. Nat. Genet. (2002) [Pubmed]
  4. The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures. Abu-Abed, S., Dollé, P., Metzger, D., Beckett, B., Chambon, P., Petkovich, M. Genes Dev. (2001) [Pubmed]
  5. Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation. Lalani, S.R., Safiullah, A.M., Fernbach, S.D., Harutyunyan, K.G., Thaller, C., Peterson, L.E., McPherson, J.D., Gibbs, R.A., White, L.D., Hefner, M., Davenport, S.L., Graham, J.M., Bacino, C.A., Glass, N.L., Towbin, J.A., Craigen, W.J., Neish, S.R., Lin, A.E., Belmont, J.W. Am. J. Hum. Genet. (2006) [Pubmed]
  6. Sox9 is required for cartilage formation. Bi, W., Deng, J.M., Zhang, Z., Behringer, R.R., de Crombrugghe, B. Nat. Genet. (1999) [Pubmed]
  7. An RNA recognition motif in Wilms' tumour protein (WT1) revealed by structural modelling. Kennedy, D., Ramsdale, T., Mattick, J., Little, M. Nat. Genet. (1996) [Pubmed]
  8. Expression of a linear Sry transcript in the mouse genital ridge. Jeske, Y.W., Bowles, J., Greenfield, A., Koopman, P. Nat. Genet. (1995) [Pubmed]
  9. WT-1 is required for early kidney development. Kreidberg, J.A., Sariola, H., Loring, J.M., Maeda, M., Pelletier, J., Housman, D., Jaenisch, R. Cell (1993) [Pubmed]
  10. Temporally-regulated retinoic acid depletion produces specific neural crest, ocular and nervous system defects. Dickman, E.D., Thaller, C., Smith, S.M. Development (1997) [Pubmed]
  11. 5 alpha-reduced androgens play a key role in murine parturition. Mahendroo, M.S., Cala, K.M., Russell, D.W. Mol. Endocrinol. (1996) [Pubmed]
  12. Inhibition of Matrix Metalloproteinases Protects Mice from Ascending Infection and Chronic Disease Manifestations Resulting from Urogenital Chlamydia muridarum Infection. Imtiaz, M.T., Schripsema, J.H., Sigar, I.M., Kasimos, J.N., Ramsey, K.H. Infect. Immun. (2006) [Pubmed]
  13. The marsupial male: a role model for sexual development. Renfree, M.B., Harry, J.L., Shaw, G. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1995) [Pubmed]
  14. Steroid-induced urogenital tract changes and urine retention in laboratory rodents. Buhl, A.E., Yuan, Y.D., Cornette, J.C., Frielink, R.D., Knight, K.A., Ruppel, P.L., Kimball, F.A. J. Urol. (1985) [Pubmed]
  15. A mouse zinc finger gene which is transiently expressed during spermatogenesis. Cunliffe, V., Koopman, P., McLaren, A., Trowsdale, J. EMBO J. (1990) [Pubmed]
  16. Structure of the human villin gene. Pringault, E., Robine, S., Louvard, D. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  17. Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development. Grimmond, S., Van Hateren, N., Siggers, P., Arkell, R., Larder, R., Soares, M.B., de Fatima Bonaldo, M., Smith, L., Tymowska-Lalanne, Z., Wells, C., Greenfield, A. Hum. Mol. Genet. (2000) [Pubmed]
  18. Multiple, distant Gata2 enhancers specify temporally and tissue-specific patterning in the developing urogenital system. Khandekar, M., Suzuki, N., Lewton, J., Yamamoto, M., Engel, J.D. Mol. Cell. Biol. (2004) [Pubmed]
  19. The LIM homeobox gene Lhx9 is essential for mouse gonad formation. Birk, O.S., Casiano, D.E., Wassif, C.A., Cogliati, T., Zhao, L., Zhao, Y., Grinberg, A., Huang, S., Kreidberg, J.A., Parker, K.L., Porter, F.D., Westphal, H. Nature (2000) [Pubmed]
  20. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Langermann, S., Palaszynski, S., Barnhart, M., Auguste, G., Pinkner, J.S., Burlein, J., Barren, P., Koenig, S., Leath, S., Jones, C.H., Hultgren, S.J. Science (1997) [Pubmed]
  21. Epithelial-mesenchymal interactions in prostatic development. I. morphological observations of prostatic induction by urogenital sinus mesenchyme in epithelium of the adult rodent urinary bladder. Cunha, G.R., Fujii, H., Neubauer, B.L., Shannon, J.M., Sawyer, L., Reese, B.A. J. Cell Biol. (1983) [Pubmed]
  22. Epithelial-mesenchymal interactions in prostatic development. II. Biochemical observations of prostatic induction by urogenital sinus mesenchyme in epithelium of the adult rodent urinary bladder. Neubauer, B.L., Chung, L.W., McCormick, K.A., Taguchi, O., Thompson, T.C., Cunha, G.R. J. Cell Biol. (1983) [Pubmed]
  23. Mouse A-myb encodes a trans-activator and is expressed in mitotically active cells of the developing central nervous system, adult testis and B lymphocytes. Trauth, K., Mutschler, B., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Klempnauer, K.H. EMBO J. (1994) [Pubmed]
  24. Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression. Ide, H., Seligson, D.B., Memarzadeh, S., Xin, L., Horvath, S., Dubey, P., Flick, M.B., Kacinski, B.M., Palotie, A., Witte, O.N. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  25. Induction of abnormal epithelial changes by estrogen in neonatal mouse vaginal transplants. Iguchi, T., Ostrander, P.L., Mills, K.T., Bern, H.A. Cancer Res. (1985) [Pubmed]
  26. Malignant transformation in a nontumorigenic human prostatic epithelial cell line. Hayward, S.W., Wang, Y., Cao, M., Hom, Y.K., Zhang, B., Grossfeld, G.D., Sudilovsky, D., Cunha, G.R. Cancer Res. (2001) [Pubmed]
  27. Urogenital carcinogenesis in female CD1 mice induced by in utero arsenic exposure is exacerbated by postnatal diethylstilbestrol treatment. Waalkes, M.P., Liu, J., Ward, J.M., Powell, D.A., Diwan, B.A. Cancer Res. (2006) [Pubmed]
  28. Characterization of a human, sex steroid-responsive transitional cell carcinoma maintained as a tumor line (R198) in athymic nude mice. Reid, L.M., Leav, I., Kwan, P.W., Russell, P., Merk, F.B. Cancer Res. (1984) [Pubmed]
  29. Changes in the reproductive system of male mice immunized with a GnRH-analogue conjugated to mycobacterial hsp70. Hannesdóttir, S.G., Han, X., Lund, T., Singh, M., Van Der Zee, R., Roitt, I.M., Delves, P.J. Reproduction (2004) [Pubmed]
  30. BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling. Grishina, I.B., Kim, S.Y., Ferrara, C., Makarenkova, H.P., Walden, P.D. Dev. Biol. (2005) [Pubmed]
  31. Lbx2, a novel murine homeobox gene related to the Drosophila ladybird genes is expressed in the developing urogenital system, eye and brain. Chen, F., Liu, K.C., Epstein, J.A. Mech. Dev. (1999) [Pubmed]
  32. Sonic hedgehog signaling regulates the expression of insulin-like growth factor binding protein-6 during fetal prostate development. Lipinski, R.J., Cook, C.H., Barnett, D.H., Gipp, J.J., Peterson, R.E., Bushman, W. Dev. Dyn. (2005) [Pubmed]
  33. Defects of urogenital development in mice lacking Emx2. Miyamoto, N., Yoshida, M., Kuratani, S., Matsuo, I., Aizawa, S. Development (1997) [Pubmed]
  34. Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Lamm, M.L., Podlasek, C.A., Barnett, D.H., Lee, J., Clemens, J.Q., Hebner, C.M., Bushman, W. Dev. Biol. (2001) [Pubmed]
  35. Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice. Cui, S., Ross, A., Stallings, N., Parker, K.L., Capel, B., Quaggin, S.E. Development (2004) [Pubmed]
  36. Differential expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivators steroid receptor coactivator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse. Jain, S., Pulikuri, S., Zhu, Y., Qi, C., Kanwar, Y.S., Yeldandi, A.V., Rao, M.S., Reddy, J.K. Am. J. Pathol. (1998) [Pubmed]
  37. Sonic hedgehog activates mesenchymal Gli1 expression during prostate ductal bud formation. Lamm, M.L., Catbagan, W.S., Laciak, R.J., Barnett, D.H., Hebner, C.M., Gaffield, W., Walterhouse, D., Iannaccone, P., Bushman, W. Dev. Biol. (2002) [Pubmed]
  38. Regulation of metanephric kidney development by growth/differentiation factor 11. Esquela, A.F., Lee, S.J. Dev. Biol. (2003) [Pubmed]
  39. p63 regulates commitment to the prostate cell lineage. Signoretti, S., Pires, M.M., Lindauer, M., Horner, J.W., Grisanzio, C., Dhar, S., Majumder, P., McKeon, F., Kantoff, P.W., Sellers, W.R., Loda, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  40. Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Benson, G.V., Lim, H., Paria, B.C., Satokata, I., Dey, S.K., Maas, R.L. Development (1996) [Pubmed]
  41. E-7869 (R-flurbiprofen) inhibits progression of prostate cancer in the TRAMP mouse. Wechter, W.J., Leipold, D.D., Murray, E.D., Quiggle, D., McCracken, J.D., Barrios, R.S., Greenberg, N.M. Cancer Res. (2000) [Pubmed]
  42. Müllerian inhibiting substance production and testicular migration and descent in the pouch young of a marsupial. Hutson, J.M., Shaw, G., O, W.S., Short, R.V., Renfree, M.B. Development (1988) [Pubmed]
  43. Establishment and characterization of conditionally immortalized cells from the mouse urogenital ridge. Capel, B., Hawkins, J.R., Hirst, E., Kioussis, D., Lovell-Badge, R. J. Cell. Sci. (1996) [Pubmed]
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