Abstract

The main objective of Core 9003 is to generated transgenic mice that are instrumental for Projects 4 and 5; to understand the role of neurotrophic factors, cholinergic and glutabminergic pathways in learning and memory, all of which are relevant to the biology of Alzheimer~s Disease. Furthermore these mice will facilitate Project 1 to develop a better gene transfer system in the brain. We will produce transgenic mice via microinjecting DNA into the pronucleus of one-cell embryos and gene targeting in mouse embryonic stem (ES) cells. We will be assisted by Core 9001 in the production of adenoviruses expressing the Cre recombinase that will be used to generate conditional mutant ES cell clones.
The specific aims are: 1. To generate transgenic mice by DNA microinjection. 2. To test reagents, maintain ES cell lines, and generate feeder cells for cultivating embryos and ES cells. 3. To generate null and conditional mutant ES cell lines by homologous recombination. 4. To generate chimeras for establishing germ- line mutant mice on an outbred or 129 inbred genetic background.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG010435-09
Application #
6098380
Study Section
Project Start
1999-03-01
Project End
2000-02-29
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Nagahara, Alan H; Wilson, Bayard R; Ivasyk, Iryna et al. (2018) MR-guided delivery of AAV2-BDNF into the entorhinal cortex of non-human primates. Gene Ther 25:104-114
Chen, Zhijiang; Donnelly, Christopher R; Dominguez, Bertha et al. (2017) p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling. Cell Rep 21:707-720
Hirai, Maretoshi; Arita, Yoh; McGlade, C Jane et al. (2017) Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation. J Clin Invest 127:569-582
Overk, Cassia; Masliah, Eliezer (2017) Perspective on the calcium dyshomeostasis hypothesis in the pathogenesis of selective neuronal degeneration in animal models of Alzheimer's disease. Alzheimers Dement 13:183-185
Spencer, Brian; Desplats, Paula A; Overk, Cassia R et al. (2016) Reducing Endogenous ?-Synuclein Mitigates the Degeneration of Selective Neuronal Populations in an Alzheimer's Disease Transgenic Mouse Model. J Neurosci 36:7971-84
Xu, Jiqing; de Winter, Fred; Farrokhi, Catherine et al. (2016) Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer's disease model. Sci Rep 6:31692
Spencer, Brian; Potkar, Rewati; Metcalf, Jeff et al. (2016) Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease. J Biol Chem 291:1905-20
Wang, Ling; Conner, James M; Nagahara, Alan H et al. (2016) Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets. Proc Natl Acad Sci U S A 113:2750-5
Valera, Elvira; Masliah, Eliezer (2016) Combination therapies: The next logical Step for the treatment of synucleinopathies? Mov Disord 31:225-34
Kratter, Ian H; Zahed, Hengameh; Lau, Alice et al. (2016) Serine 421 regulates mutant huntingtin toxicity and clearance in mice. J Clin Invest 126:3585-97

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