Animal model for preeclampsia

• US 20040133929A1
• Filed: 09/19/2003
• Published: 07/08/2004
• Est. Priority Date: 09/19/2002
• Status: Active Grant

• Current Assignee: University of Iowa Research Foundation
• Original Assignee: University of Iowa Research Foundation
• Inventors: Davisson, Robin L.
• Granted Patent: US 7,045,674 B2
• Time in Patent Office: Days
• US Class Current: 800/3
• CPC Class Codes: A61K 49/0008 Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure

Abstract

The invention provides an animal model for preeclampsia that allows candidate compounds to be screened for their ability to treat preeclampsia.

Claims

1. A method for screening for compounds useful for the treatment or amelioration of preeclampsia and/or the symptoms thereof comprising:

inducing preeclampsia in an animal with a BPH/5 phenotype;

administering a test compound to the animal; and

monitoring the animal for amelioration or elimination of preeclampsia or its symptoms, wherein amelioration or elimination of preeclampsia or its symptoms in the animal indicates usefulness of the compound for the treatment of preeclampsia.

2. The method of claim 1, wherein the animal is a mouse.

3. The method of claim 2, wherein the mouse is a BPH/5 mouse.

4. The method of claim 3, wherein preeclampsia is induced by mating the BPH/5 mouse with another mouse such that the BPH/5 mouse becomes pregnant.

5. A method for screening for compounds useful for the treatment of preeclampsia comprising:

mating a BPH/5 mouse with another mouse such that the BPH/5 mouse becomes pregnant;

administering a test compound to the pregnant BPH/5 mouse; and

monitoring the pregnant BPH/5 mouse for amelioration or elimination of preeclampsia, wherein amelioration or elimination of preeclampsia in the pregnant BPH/5 mouse indicates usefulness of the compound for the treatment of preeclampsia.

21. An animal model produced according to the method of claim 5.

6. A method of detecting placental abnormalities in a animal suffering from preeclampsia comprising:

inducing preeclampsia in an animal having a BPH/5 phenotype; and

monitoring the expression of a gene product wherein a downregulation of expression of the gene is indicative of impaired placental development associated with preeclampsia.

7. The method of claim 6 wherein said gene is selected from the group consisting of Placental Lactogen (PL) 1, Placental Lactogen (PL) 2, Insulin-like Growth Factor 2, Proliferin (PRF), Proliferin-related protein (Prp), VEGF, sFlt-1, and Adrenomedulin.

8. The method of claim 7, wherein the animal is a mouse.

9. The method of claim 8, wherein the mouse is BPH/5 mouse.

10. A method of producing an animal that exhibits symptoms of preeclampsia comprising:

inducing pregnancy in an BPH/5 animal;

evaluating the presence pathological features characterized by placental morphological abnormalities, downregulation of genes associated with placental angiogenesis, and a decrease in uterine blood flow, whereby these features is indicative of the animal having preeclampsia relative to a control animal.

11. The method of claim 10, wherein the animal is a mouse.

12. The method of claim 11, wherein the mouse is BPH/5 mouse.

13. A method of screening a candidate compound for alleviating preeclampsia, said method comprising:

inducing preeclampsia in an animal;

administering a compound to said animal; and

comparing the induced preeclampsia condition in said animal with the induced preeclampsia condition in a control animal that did not receive said candidate compound, wherein an amelioration or elimination in the preeclampsia condition of the treated animal is indicative of the alleviating activity of said candidate compound.

14. The method of claim 13, wherein the animal is a mouse.

15. The method of claim 14, wherein the mouse is BPH/5 mouse.

16. A method of screening a candidate compound for the prevention of preeclampsia, said method comprising:

administering a compound to an animal with a BPH/5 phenotype;

inducing pregnancy in an animal; and

comparing the pregnant condition in said animal with said candidate agent with a pregnant control BPH/5 exhibiting preeclampsia, wherein the prevention or reduction of the affects of the preeclampsia condition of the treated animal is indicative of the alleviating activity of said candidate compound.

17. A method of screening a candidate compound for alleviating the symptoms of preeclampsia, said method comprising:

inducing preeclampsia in a BPH/5 phenotype animal;

administering a compound to said animal; and

comparing the induced preeclampsia condition in said animal with the induced preeclampsia condition in a control animal that did not receive said candidate compound,

wherein an amelioration or elimination in the preeclampsia condition of the treated animal is indicative of the alleviating activity of said candidate compound.

18. The method of claim 17, wherein said animal is a mouse.

19. The method of claim 18 wherein said animal is a BPH/5 mouse.

20. An animal model for identifying agents which alleviate the symptoms of, treat, reduce the severity of, or prevent preeclampsia comprising:

a pregnant BPH/5 mouse, and

an agent suspected of alleviate the symptoms of, treat, reduce the severity of or prevent preeclampsia which has been introduced to said mouse.