WO 2009/042645 A2 - The Use Of Mice Predisposed To Develop Ulcerative Colitis And Colon Cancer To Develop Metabolic Profiles Associated With Same - The Lens

The Use Of Mice Predisposed To Develop Ulcerative Colitis And Colon Cancer To Develop Metabolic Profiles Associated With Same

Published: Apr 2, 2009
Earliest Priority: Sep 24 2007
Family: 7
Cited Works: 0
Cited by: 0
Cites: 0
Sequences: 4
Additional Info: Full text Published Sequence

Abstract

The instant invention is based, at least in part, on the discovery that mice deficient in T-bet develop a form of ulcerative colitis that is transmissible to genetically intact hosts. Accordingly, these animals are useful in the development of metabolic profiles that will enhance the predisposition of a subject to develop ulcerative colitis and/or colon cancer and are useful in the identification of targets for therapeutic intervention.

Claims

A method for identifying a metabolic profile associated with development or progression of ulcerative colitis or colorectal cancer comprising, providing a biological sample derived from an animal which develops spontaneous ulcerative colitis; determining a metabolic profile of the biological sample from the animal; and comparing the metabolic profile of the biological sample from the animal to a standard profile derived from a biological sample of an animal, thereby identifying a metabolic profile associated with development or progression of ulcerative colitis or colorectal cancer.
A method for identifying a metabolic profile associated with development or progression of ulcerative colitis or colorectal cancer comprising, providing a biological sample derived from an animal which develops transmissible ulcerative colitis; determining a metabolic profile of the biological sample from the animal; and comparing the metabolic profile of the biological sample from the animal to a standard profile derived from a biological sample of a animal, thereby identifying a metabolic profile associated with development or progression of ulcerative colitis or colorectal cancer.
A method for determining the predisposition of a subject to develop ulcerative colitis, said method comprising determining the activity of T-bet in a biological sample derived from the subject and comparing the activity of T-bet in said sample to the activity of T-bet in an appropriate control sample, wherein a decrease in the activity of T-bet in the sample relative to the activity of T-bet in the control sample indicates that the subject is at risk of developing ulcerative colitis, thereby determining the predisposition of a subject to develop ulcerative colitis.
A method for determining the predisposition of a subject to develop colon cancer, said method comprising determining the activity of T-bet in a biological sample derived from the subject and comparing the activity of T-bet in said sample to the activity of T-bet in an appropriate control sample, wherein a decrease in the activity of T-bet in the sample relative to the activity of T-bet in the control sample indicates that the subject is at risk of developing colon cancer, thereby determining the predisposition of a subject to develop colon cancer.
The method of claim 4, further comprising determining a metabolic profile of the subject identified as being at risk of developing ulcerative colitis and comparing the metabolic profile of the subject to a standard profile derived from a biological sample of a control subject.
The method of claim 3, further comprising determining a metabolic profile of the subject identified as being at risk of developing colorectal cancer and comparing the metabolic profile of the subject to a standard profile derived from a biological sample of a control subject.
A method for determining the predisposition of a subject to develop ulcerative colitis or colon cancer in a subject that would benefit from increased T-bet activity comprising, providing a biological sample derived from the subject ; determining a metabolic profile of the biological sample from the subject; and comparing the metabolic profile of the biological sample from the subject to a metabolic profile associated with ulcerative colitis or the development of ulcerative colitis, identifying similarities in the metabolic profiles, to thereby determine the predisposition of a subject to develop ulcerative colitis or colon cancer in a subject that would benefit from increased T-bet activity.
A method for identifying a metabolic profile associated with development or progression of ulcerative colitis or colorectal cancer comprising, providing a biological sample derived from a subject that would benefit from increased T-bet activity; determining a metabolic profile of the biological sample from the subject; and comparing the metabolic profile of the biological sample from the subject to a standard profile derived from a biological sample of a control, thereby identifying a metabolic profile associated with development and/or progression of ulcerative colitis and/or colorectal cancer.
The method of claim 1 or 2, wherein the animal is a mouse.
The method of claim 9, wherein the mouse spontaneously develops ulcerative colitis.
The method of claim 10, wherein the mouse is a TRUC mouse.
The method of claim 9, wherein the animal is genetically intact and has been cohoused with an animal that develops transmissible ulcerative colitis.
The method of claim 12, wherein the animal has been nursed by an animal deficient in T-bet.
The method of any one of claims 1, 2, 7, or 8, wherein the metabolic profile is determined by Mass Spectroscopy (MS) Detectors, Pyrolysis Mass Spectrometry, Nuclear Magnetic Resonance (NMR) Detectors, Refractive Index (RI), Ultra- Violet (UV) Detectors, Fluorescent Detectors, Radiochemical
Detection,Electrochemical Detection, Light Scattering (LS) Detectors, Fourier Transform Infrared Spectroscopy (FT-IR), and Dispersive Raman Spectroscopy.