University of California

Thomas L Innerarity

Robert V Farese, Jr

Sylvaine Cases

Erwin H Ludwig

Shinya Yamanaka

Xiaobing Qian

The present invention relates to the study and control of atherosclerosis through the modulation of LDL-proteoglycan binding at Site B (amino acids 3359&#x2013;3369) of the apo-B100 protein in LDL. The invention encompasses methods of identifying compounds which modulate LDL-proteoglycan binding, methods of identifying compounds which modulate atherosclerotic lesion formation, and methods of modulating the formation of atherosclerotic lesions. The invention also encompasses mutant apo-B100 proteins and LDL which exhibit reduced proteoglycan binding while maintaining LDL-receptor binding, polynucleotides which encode these apo-B100 proteins, as well as cells and animals which express the mutant apo-B100 proteins.

Methods and tools for identifying compounds which modulate atherosclerosis by impacting LDL-proteoglycan binding

The present invention relates to the study and control of atherosclerosis through the modulation of LDL-proteoglycan binding at Site B (amino acids 3359-3369) of the apo-B100 protein in LDL. The invention encompasses methods of identifying compounds which modulate LDL-proteoglycan binding, methods of identifying compounds which modulate atherosclerotic lesion formation, and methods of modulating the formation of atherosclerotic lesions. The invention also encompasses mutant apo-B100 proteins and LDL which exhibit reduced proteoglycan binding while maintaining LDL-receptor binding, polynucleotides which encode these apo-B100 proteins, as well as cells and animals which express the mutant apo-B100 proteins.

The present invention provides isolated an polynucleotide comprising a polymorphic nucleotide sequence from a diacylglycerol acyltransferase (DGAT) gene, wherein at least one a polymorphism is associated with a condition relating to DGAT activity. The invention further provides diagnostic assays for detecting the presence in a nucleic acid sample of a polymorphism in a DGAT gene that is associated with a condition relating to DGAT activity, and for detecting a propensity to develop a condition associated with DGAT activity. The invention further provides treatment methods.

Polymorphisms in a diacylglycerol acyltransferase gene, and methods of use thereof

The expression of APOBEC-1 in the liver of transgenic mice can cause liver dysplasia and liver tumors, and the expression of human APOBEC-1 in the intestine, stomach, or brain can cause obesity. Promiscuous editing of other mRNAs is correlated to these phenotypic changes. The instant invention discloses novel techniques for detecting aberrantly edited mRNAs, and hence, genes responsible for non-wild type phenotypes.

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Lafayette, CA, United States of America

Thomas L Innerarity