This Core will maintain existing lines of transgenic (and other) mice and will provide animals of various ages (from embryos to aged adults) to projects within this program. The Core is organized with two dominant Specific Aims: ? Maintaining transgenic mice relevant to the study of presenilin biology and Alzheimer disease and to provide animals of various ages (from embryos to aged adults) to investigators. ? Organizing and coordinating animal requirements across the individual projects to make maximal and efficient usage of this important, expensive and limited resource. Animals to be covered in this Core include locally generated mice expressing mutant (M146L) or wild type forms of human PS1, wild type human APLP2, as well as animals generated in other laboratories. The later include several transgenic models in which A_ deposition occurs as the consequence of a mutant form of APP (with or without mutant forms of PS1). These lines include the Tg2576 line of mice [over-expression of APP-Sw alone], the APPswe/PS1dE9 line of mice [with over-expression of both APPSw and the exon 9 deleted form of PS1] and the J20 line of mice [over-expression of APP-Sw,Ind ]. The Core will also work with investigators of the Program Project to develop new lines of mice relevant to their projects should these become relevant. Thus a potential third Specific Aim of the Core is to: ? Participate, in collaboration with the relevant investigator(s), in developing and characterizing and utilizing new mouse models. By consolidation of efforts involving animals, the Program Project seeks efficient use of animal resources, through the coordination of requests from different investigators and sharing of the animals when possible. This will help to keep animal numbers and costs are kept as low as possible while ensuring that, within the limits of colony space, the needs of investigators in all projects are met. Animals from this Core are also made available, as possible, to investigators outside of the Program Project.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG015379-15
Application #
8381468
Study Section
Special Emphasis Panel (ZAG1-ZIJ-3)
Project Start
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
15
Fiscal Year
2012
Total Cost
$64,041
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Zoltowska, Katarzyna Marta; Berezovska, Oksana (2017) Dynamic Nature of presenilin1/?-Secretase: Implication for Alzheimer's Disease Pathogenesis. Mol Neurobiol :
Gong, Yi; Sasidharan, Nikhil; Laheji, Fiza et al. (2017) Microglial dysfunction as a key pathological change in adrenomyeloneuropathy. Ann Neurol 82:813-827
Kara, Eleanna; Marks, Jordan D; Fan, Zhanyun et al. (2017) Isoform- and cell type-specific structure of apolipoprotein E lipoparticles as revealed by a novel Forster resonance energy transfer assay. J Biol Chem 292:14720-14729
Raven, Frank; Ward, Joseph F; Zoltowska, Katarzyna M et al. (2017) Soluble Gamma-secretase Modulators Attenuate Alzheimer's ?-amyloid Pathology and Induce Conformational Changes in Presenilin 1. EBioMedicine 24:93-101
Wagner, Steven L; Rynearson, Kevin D; Duddy, Steven K et al. (2017) Pharmacological and Toxicological Properties of the Potent Oral ?-Secretase Modulator BPN-15606. J Pharmacol Exp Ther 362:31-44
Yang, Ting; Li, Shaomin; Xu, Huixin et al. (2017) Large Soluble Oligomers of Amyloid ?-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate. J Neurosci 37:152-163
Ward, Joseph; Wang, Haizhi; Saunders, Aleister J et al. (2017) Mechanisms that synergistically regulate ?-secretase processing of APP and A?-? protein levels: relevance to pathogenesis and treatment of Alzheimer's disease. Discov Med 23:121-128
Zoltowska, Katarzyna Marta; Maesako, Masato; Lushnikova, Iryna et al. (2017) Dynamic presenilin 1 and synaptotagmin 1 interaction modulates exocytosis and amyloid ? production. Mol Neurodegener 12:15
Bolduc, D M; Selkoe, D J; Wolfe, M S (2017) Enzymatic Assays for Studying Intramembrane Proteolysis. Methods Enzymol 584:295-308
Williamson, Rebecca L; Laulagnier, Karine; Miranda, André M et al. (2017) Disruption of amyloid precursor protein ubiquitination selectively increases amyloid ? (A?) 40 levels via presenilin 2-mediated cleavage. J Biol Chem 292:19873-19889

Showing the most recent 10 out of 139 publications