Title:
MODEL ANIMAL FOR PREGNANCY-INDUCED HYPERTENSION SYNDROME, AND TREATMENT METHOD THEREFOR
Document Type and Number:
WIPO Patent Application WO/2011/108711
Kind Code:
A1
Abstract:
Provided are: a model animal which closely models actual clinical cases of disorders such as pregnancy-induced hypertension syndrome; a method for producing said model animal; a screening method using said model animal to screen candidate therapeutic compounds for disorders such as pregnancy-induced hypertension syndrome; and a therapeutic agent for disorders such as pregnancy-induced hypertension syndrome. In order to provide the above, a lentiviral vector was used on a mouse placenta to create a non-human animal that specifically expresses human sFLT1. The resulting model animal exhibited symptoms extremely close to actual human clinical cases; namely: hypertension, placental dysfunction, intrauterine fetal growth retardation, glomerulosclerosis, and proteinuria during pregnancy, with said symptoms exhibiting improvement following delivery. Furthermore, administering pravastatin to the model animal caused amelioration of disorders such as pregnancy-induced hypertension syndrome due to activation of placenta growth factor (PlGF), which is antagonistic towards sFLT1.
Inventors:
OKABE MASARU (JP)
IKAWA MASAHITO (JP)
KIMURA TADASHI (JP)
KUMASAWA KEIICHI (JP)
IKAWA MASAHITO (JP)
KIMURA TADASHI (JP)
KUMASAWA KEIICHI (JP)
Application Number:
PCT/JP2011/055087
Publication Date:
September 09, 2011
Filing Date:
March 04, 2011
Export Citation:
Assignee:
OKABE MASARU (JP)
IKAWA MASAHITO (JP)
FUSO PHARMACEUTICAL IND (JP)
KIMURA TADASHI (JP)
KUMASAWA KEIICHI (JP)
IKAWA MASAHITO (JP)
FUSO PHARMACEUTICAL IND (JP)
KIMURA TADASHI (JP)
KUMASAWA KEIICHI (JP)
International Classes:
C12N15/09; A01K67/027; A61K38/27; A61K48/00; A61P9/12; A61P13/12; A61P15/00
Domestic Patent References:
| WO2007020786A1 | 2007-02-22 |
Foreign References:
| JP2007518769A | 2007-07-12 | |||
| JP2009538831A | 2009-11-12 |
Other References:
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MULLIGAN ET AL., NATURE, vol. 277, 1979, pages 108
MIZUSHIMA ET AL., NUCLEIC ACIDS RES., vol. 18, 1990, pages 5322
EBERT, K. M., BIO/TECHNOLOGY, vol. 12, 1994, pages 699 - 702
SUSUMU, M. ET AL., NATURE, vol. 315, 1985, pages 592 - 594
JULIAN K.-C. MA ET AL., EUR. J. IMMUNOL., vol. 24, 1994, pages 131 - 138
NAT GENET., vol. 25, no. 2, June 2000 (2000-06-01), pages 217 - 22
NAT. BIOTECHNOL., vol. 25, no. 2, February 2007 (2007-02-01), pages 233 - 7
PHARMACOL THER., vol. 122, no. 1, 23 January 2009 (2009-01-23), pages 30 - 43
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BLOOD., vol. 113, no. 17, 20 February 2009 (2009-02-20), pages 4101 - 9
HYPERTENSION., vol. 50, no. 4, 27 August 2007 (2007-08-27), pages 686 - 92
HYPERTENSION, vol. 54, no. 5, 28 September 2009 (2009-09-28), pages 1129 - 35
AM J PHYSIOL HEART CIRC PHYSIOL., vol. 294, no. 3, 11 January 2008 (2008-01-11), pages 3 81 - 7
REPROD TOXICOL., vol. 26, no. 2, 1 July 2008 (2008-07-01), pages 175 - 7
BR J CLIN PHARMACOL., vol. 64, no. 4, 15 May 2007 (2007-05-15), pages 496 - 509
REPROD TOXICOL., vol. 10, no. 6, November 1996 (1996-11-01), pages 439 - 46
See also references of EP 2543729A4
HIROMASA SUZUKI ET AL.: "sFlt-1 Kajo Hatsugen ni yoru Ninshin Koketsuatsu Jinsho-yo Mouse Model ni Okeru, Kekkan Shinsei Inshi Toyo ni yoru Kecchu NO eno Eikyo", ACTA OBSTETRICA ET GYNAECOLOGIA JAPONICA, vol. 62, no. 2, February 2010 (2010-02-01), pages 492
MAYNARD SE ET AL.: "Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia", J CLIN INVEST., vol. 111, no. 5, March 2003 (2003-03-01), pages 649 - 658, XP002570650
KODAMA, Y. ET AL.: "Atorvastatin Increases Plasma sFlt-1 and Decreases VEGF and P1GF in Association with Improvement of Ventricular Function in Acute Myocardial Infarction", CIRC J, vol. 71, no. SUPL.1, 2007, pages 670
KODAMA, Y. ET AL.: "Atorvastatin increases plasma soluble Fms-like tyrosine kinase-1 and decreases vascular endothelial growth factor and placental growth factor in association with improvement of ventricular function in acute myocardial infarction", JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, vol. 48, no. 1, 2006, pages 43 - 50, XP028006623
LOBODA, A. ET AL.: "Angiogenic transcriptome of human microvascular endothelial cells: Effect of hypoxia, modulation by atorvastatin", VASCULAR PHARMACOLOGY, vol. 44, no. 4, 2006, pages 206 - 214, XP024969976
KUMASAWA, K. ET AL.: "Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model", PROC NATL ACAD SCI USA, vol. 108, no. 4, 25 January 2011 (2011-01-25), pages 1451 - 1455, XP002701225
LANCET., vol. 367, no. 9516, 1 April 2006 (2006-04-01), pages 1066 - 74
J CLIN INVEST., vol. 111, no. 5, March 2003 (2003-03-01), pages 649 - 58
N ENGL J MED., vol. 350, no. 7, 12 February 2004 (2004-02-12), pages 672 - 83
LANCET, vol. 367, no. 9516, 1 April 2006 (2006-04-01), pages 1066 - 74
N ENGL J MED., vol. 350, no. 7, 5 February 2004 (2004-02-05), pages 672 - 83
NAT BIOTECHNOL., vol. 25, no. 2, February 2007 (2007-02-01), pages 233 - 7
GENESIS, vol. 47, no. 12, December 2009 (2009-12-01), pages 793 - 8
SHIBUYA, CELL STRUCTURE AND FUNCTION, vol. 26, 2001, pages 25 - 35
"Membrane Fixation of Vascular Endothelial Growth Factor Receptor 1 Ligand-Binding Domain Is Important for Vasculogenesis and Angiogenesis in Mice", MOLECULAR AND CELLULAR BIOLOGY, vol. 25, no. 1, January 2005 (2005-01-01), pages 346 - 354
"Manipulating the mouse embryo, a laboratory manual", COLD SPRING HARBOR LABORATORY PRESS, pages: 201 - 203
"Manipulating the mouse embryo, a laboratory manual", COLD SPRING HARBOR LABORATORY PRESS, pages: 485 - 486
"Manipulating the mouse embryo, a laboratory manual", COLD SPRING HARBOR LABORATORY PRESS, pages: 731
HUM. REPROD., vol. 5, 1990, pages 7 - 13
HUM. REPROD., vol. 15, 2000, pages 1061 - 1064
DEVELOPMENTAL BIOLOGY, vol. 250, 2002, pages 348 - 357
MOLECULAR THERAPY, vol. 8, 2003, pages 666 - 673
SOUTHERN, E. M., JOURNAL OF MOLECULAR BIOLOGY, vol. 98, 1975, pages 503
SAIKI, R. K. ET AL., SCIENCE, vol. 230, 1985, pages 1350 - 1354
SAIKI, R. K. ET AL., SCIENCE, vol. 239, 1988, pages 487 - 491
KARLIN; ALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 87, 1990, pages 2264 - 2268
PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 5873
"Manipulating the mouse embryo, a laboratory manual", COLD SPRING HARBOR LABORATORY PRESS, pages: 263 - 271
HAFEZ: "Theriogenology", 1992, SHOTEN, article "Bovine Embryo Transplantation"
JOURNAL OF LIPID RESEARCH, vol. 33, 1992
WARD ET AL., NATURE, vol. 341, 1989, pages 544 - 546
FASEB J., vol. 6, 1992, pages 2422 - 2427
BETTER ET AL., SCIENCE, vol. 240, 1988, pages 1041 - 1043
LEI, S. P. ET AL., J. BACTERIOL., vol. 169, 1987, pages 4379
NUCLEIC ACIDS RES., vol. 18, no. 17, 1990, pages 5322
MULLIGAN ET AL., NATURE, vol. 277, 1979, pages 108
MIZUSHIMA ET AL., NUCLEIC ACIDS RES., vol. 18, 1990, pages 5322
EBERT, K. M., BIO/TECHNOLOGY, vol. 12, 1994, pages 699 - 702
SUSUMU, M. ET AL., NATURE, vol. 315, 1985, pages 592 - 594
JULIAN K.-C. MA ET AL., EUR. J. IMMUNOL., vol. 24, 1994, pages 131 - 138
NAT GENET., vol. 25, no. 2, June 2000 (2000-06-01), pages 217 - 22
NAT. BIOTECHNOL., vol. 25, no. 2, February 2007 (2007-02-01), pages 233 - 7
PHARMACOL THER., vol. 122, no. 1, 23 January 2009 (2009-01-23), pages 30 - 43
CIRCULATION, vol. 105, no. 6, 12 February 2002 (2002-02-12), pages 739 - 45
BLOOD., vol. 113, no. 17, 20 February 2009 (2009-02-20), pages 4101 - 9
HYPERTENSION., vol. 50, no. 4, 27 August 2007 (2007-08-27), pages 686 - 92
HYPERTENSION, vol. 54, no. 5, 28 September 2009 (2009-09-28), pages 1129 - 35
AM J PHYSIOL HEART CIRC PHYSIOL., vol. 294, no. 3, 11 January 2008 (2008-01-11), pages 3 81 - 7
REPROD TOXICOL., vol. 26, no. 2, 1 July 2008 (2008-07-01), pages 175 - 7
BR J CLIN PHARMACOL., vol. 64, no. 4, 15 May 2007 (2007-05-15), pages 496 - 509
REPROD TOXICOL., vol. 10, no. 6, November 1996 (1996-11-01), pages 439 - 46
See also references of EP 2543729A4
Attorney, Agent or Firm:
SHIMIZU, Hatsushi et al. (JP)
Spring water Original aim (JP)
Spring water Original aim (JP)
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