Lockheed SR-71 ( A-12 YF-12 D-21 ) - Aerofax Minigraph 1 by Jay Miller

By Jay Miller

Publication by means of Miller, Jay

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The proposed work is to cross the Tg2576 mice with mice generated in 34 Amyloidosis our laboratory that carry two common alleles for human apolipoprotein E (APOE), APOE-2 and APOE-4. APOE-4 is a risk factor for AD, and APOE-2 is reported to be beneficial in somehow retarding the development of AD. The ultimate goal is to obtain two mouse lines that each carry three transgenes; one carrying APOE-4, APPSWED, and mouse APOE-knockout (E-KO); the other carrying APOE-2, APPSWED, and E-KO. In addition, we also plan to similarly use a new APPSWED transgenic line recently developed in our laboratory to cross with APOE-2 and APOE-4 mouse lines.

A mutation (IAPPS20G) in he human wildtype islet amyloid precursor protein (hIAPPWT, amylin) has been associated with premature onset NIDDM in Japanese populations, providing a direct linkage of the IAPP gene with the genesis of NIDDM. IAPP is the major component of islet cell amyloid deposits which are a hallmark of NIDDM, suggesting that islet amyloid may be involved in the pathogenesis of this disease. We demonstrated that hIAPPWT expression in COS-1 and betaTC-3 cells results in the accumulation of intracellular amyloid within the endoplasmic reticulum (ER)/Golgi and induction of apoptosis.

IAPP is the major component of islet cell amyloid deposits which are a hallmark of NIDDM, suggesting that islet amyloid may be involved in the pathogenesis of this disease. We demonstrated that hIAPPWT expression in COS-1 and betaTC-3 cells results in the accumulation of intracellular amyloid within the endoplasmic reticulum (ER)/Golgi and induction of apoptosis. The expression of IAPPS2OG in these cells results in increased cytotoxicty and this is correlated with its increased in vitro amyloidogenic character as compared to IAPPWT.

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