Biopolym. Cell. 2014; 30(2):122-128.
Genomics, Transcriptomics and Proteomics
Mice with pituitary tumor transforming gene (pttg) knockout demonstrate increased urinary space in renal corpuscles
1Varyvoda O. Yu., 1Yashchenko A. M., 1Lutsyk A. D., 1, 2Bilyy R. O., 2Afanasiev S. V., 2Filyak Ye. Z., 2Stoika R. S.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. Institute of Cell Biology, NAS of Ukraine
    14/16, Drahomanov Str., Lviv, Ukraine, 79005

Abstract

Aim. To investigate the effect of knockout of the pituitary tumor transforming gene (pttg-1) on the morphometric parameters and carbohydrate determinants of the murine renal structures. Methods. Kidneys of the knockout mice in comparison with the wild type mice of BL6/C57 strain of 1 month and 1 year age were subjected to morphometric investigation and lectin histochemistry. Morphometric study was completed using ImagePro Plus and ImageJ software. Glycoconjugates were detected by means of 8 lectins possessing different carbohydrate affinities. Results. Knockout of the pttg-1 gene was accompanied by an increased (approx. 30 %) urinary space within the renal corpuscles, enhanced exposure of the LCA and PNA receptor sites, and reduced binding of the LABA, WGA and SNA lectins. Conclusions. This study suggests the effect of the pttg-1 gene products on processing and exposure of the carbohydrates in renal tissues, apparently affecting ultrafiltration of the primary urine.
Keywords: knockout of pttg-1 gene, lectin histochemistry, renal corpuscles, morphometry, mice

References

[1] Pei L, Melmed S. Isolation and characterization of a pituitary tumor-transforming gene (pttg). Mol Endocrinol. 1997; 11(4): 433–41.
[2] Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S. Structure, expression, and function of human pituitary tumor-transforming gene (pttg). Mol Endocrinol. 1999; 13(1):156–66.
[3] Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N. The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin Med Res. 2006; 4(2):130–7.
[4] Wang Z, Yu R, Melmed S. Mice lacking pituitary tumor transforming gene show testicular and splenic hypoplasia, thymic hyperplasia, thrombocytopenia, aberrant cell cycle progression, and premature centromere division. Mol Endocrinol. 2001; 15(11): 1870–9.
[5] Kanyuka O, Filyak Ye, Sybirna N. Erythrone functional state in mice with the knockout of pttg gene. Visnyk of L'viv University, Ser Biol. 2011; Is. 56:22–27.
[6] Afanasyev S, Filak Y, Stoyka R. Effect of lack of pttg-1 on development of autoimmune processes. Stud Biol. 2011; 5(2):29–36.
[7] Zou H, McGarry TJ, Bernal T, Kirshner MW. Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science. 1999; 285(5426):418–22.
[8] Zur A, Brandeis M. Securin degradation is mediated by fzy and fzr and is required for complete chromatid separation but not for cytokinesis. EMBO J. 2001; 20(4):792–801.
[9] Yu R, Ren SG, Horwitz GA, Wang Z, Melmed S. Pituitary Tumor Transfroming Gene (pttg) regulates placental JEG-3 cell division and survival: evidence from live cell imaging. Mol Endocrinol. 2000; 14(8):1137–46.
[10] Yu R, Heaney A, Lu W, Chen J, Melmed S. Pituitary tumor-transforming gene (pttg) causes aneuploidy and p53-dependent and p53-independent apoptosis. J Biol Chem. 2000; 275(47): 36502–5.
[11] Mei J, Huang X, Zhang P. Securin is not required for cellular viability, but is required for normal growth of mouse embryonic fibroblasts. Curr Biol. 2001; 11(15):1197–201.
[12] Varyvoda OY., Filyak YuZ, Lutsyk AD, Stoika RS. Mice lacking pituitary tumor transforming gene show elevated exposure of DGalNAc carbohydrate determinants. Biopolym Cell. 2012; 28 (2):129–33.
[13] The sugar code: fundamentals of glycosciences. Ed. HJ Gabius. Weinheim: John Wiley & Sons, 2009; 597 p.
[14] Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME. Essentials of glycobiology. 2nd ed. Cold Spring Harbor: Cold Spring Harbor Lab. Press, 2009; 586 p.
[15] Lutsyk AD, Detiuk ES, Lutsyk MD. Lectins in histochemistry. Lviv: Vyshcha Shkola, 1989; 144 p.
[16] Antonyuk VO. Lectins and their resources. Lviv: Kvart, 2005; 554 p.
[17] Sharon N. Lectins: carbohydrate-specific reagents and biological recognition molecules. J Biol Chem. 2007; 282(5):2753–64.
[18] Bilyy R, Podhorodecki A, Nyk M, Stoika R, Zaichenko A, Zatryb G, Misiewicz J, Strek W. Utilization of GaN: Eu3+ nanocrystals for the detection of programmed cell death. Physica E: Low-dimensional Systems and Nanostructures. 2007; 40(6):2096–9.
[19] Bilyy R, Tomyn A, Kit Y, Podhorodecki A, Misiewicz J, Nyk M, Strek W, Stoika R. Detection of dying cells using lectin-conjugated fluorescent and luminescent nanoparticles. Materialwissenschaft Werkstofftechnik Special Issue: Nanoscience and Nanotechnology 2009; 40(4):234–7.
[20] Bilyy R, Nemesh L, Antonyuk V, Kit Y, Valchuk I, Havryluk A, Chopyak V, Stoika R. Apoptosis-related changes in plasma membrane glycoconjugates of peripheral blood lymphocytes in rheumatoid arthritis. Autoimmunity. 2009; 42(4):334–6.
[21] Roth J. Lectins for histochemical demonstration of glycans. Histochem Cell Biol. 2011; 136(1):117–30.
[22] Lutsyk A, Sogomonian E. Structural, functional, and lectin histochemical characteristics of rat ovaries and endometrium in experimental hyperand hypothyroidism. Folia Histochem Cytobiol. 2012; 50(3):331–9.
[23] Hanai T, Usuda N, Morita T, Nagata T. Light microscopic lectin histochemistry in aging mouse kidney: study of compositional changes in glycoconjugates. J Histochem Cytochem. 1994; 42 (7):897–906.
[24] Lutsyk A, Ambarova N, Antonyuk V. Diabetic alteration versus postnatal maturation of rat kidney glycoconjugates – comparative detection by lectin probes. Folia Histochem Cytobiol. 2013; 51(1):92–102.
[25] Wang Z, Melmed S. Characterization of the murine pituitary tumor transforming gene (pttg) and its promoter. Endocrinology. 2000; 141(2):763–71.
[26] Briggs MR, Kadonaga JT, Bell SP, Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986; 234(4772):47–52.
[27] Yu CY, Motamed K, Chen J, Bailey AD, Shen CK. The CACC box upstream of human embryonic epsilon globin gene binds Sp1 and is a functional promoter element in vitro and in vivo. J Biol Chem. 1991; 266(14):8907–15.
[28] Spanopoulo E, Giguere V, Grosveld F. The functional domains of the murine Thy-1 gene promoter. Mol Cell Biol. 1991; 11(4): 2216–28.
[29] Zhang D, Hetherington CJ, Tan S, Dziennis SE, Gonzales DA, Chen H, Tenen DG. Sp1 is a critical factor for the monocytic specific expression of human CD14. J Biol Chem. 1994; 269(15): 11425–34.