Genetically modified mouse models have been very useful in research on neurodegenerative disorders, and the proposed program will take maximal advantage of this valuable resource. The main goal of Core C is to help the project leaders address their research questions conclusively with the minimal number of animals and experiments possible. To achieve this goal, we propose six specific aims.
Aim 1 : Maintain all animals in a manner that ensures the reliable selection of experimental and control groups for timely distribution to the different projects. Rodents will be housed in specific-pathogen-free animal care facilities in the Gladstone building at UCSF's Mission Bay campus and in the Medical Teaching Facility at UCSD's La Jolla campus. Detailed information on these animals will be recorded in a database that is accessible to all project leaders and their coworkers via the computer networks of the Gladstone Institutes and the University of California.
Aim 2 : Breed the different lines of genetically modified mice and determine the genotype of the offspring by polymerase chain reaction (PCR). The core personnel have ample experience in genotyping genetically modified mice and maintaining complex animal databases.
Aim 3 : Receive mice from the Gladstone microinjection facility and blastocyst core and identify new genetically modified lines of mice. Gladstone and UCSD maintain state-of-the-art facilities for transgene microinjection and gene targeting.
Aim 4 : Periodically analyze all lines of mice to confirm that levels and patterns of (trans)gene expression have remained stable. Cerebral levels of transgene expression will be tested by quantitative fluorogenic PCR. The distribution of transgene expression will be characterized in collaboration with Core D. We will also collaborate closely with Core D and veterinary staff to continually optimize our protocols for the anesthesia and perfusion of animals and for the removal, dissection, and proper storage of neural tissues.
Aim 5 : Ship mice to Dr. Masliah at UCSD and to investigators at other institutions, and provide the investigators with advice on the genotyping and husbandry of the mice. We have distributed our animal models to many institutions around the world and will continue to make our models available to the scientific community.
Aim 6 : Maintain a comprehensive mouse colony database to efficiently store and manage detailed information for current and future experiments. We will continue to optimize our database to store mouse colony data in a clear and accessible manner, minimize the effort and time required to enter data, and facilitate the development of individualized modules to best suit the needs of specific investigators and studies.
|Valera, Elvira; Spencer, Brian; Mott, Jennifer et al. (2017) MicroRNA-101 Modulates Autophagy and Oligodendroglial Alpha-Synuclein Accumulation in Multiple System Atrophy. Front Mol Neurosci 10:329|
|Valera, Elvira; Spencer, Brian; Fields, Jerel A et al. (2017) Combination of alpha-synuclein immunotherapy with anti-inflammatory treatment in a transgenic mouse model of multiple system atrophy. Acta Neuropathol Commun 5:2|
|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|
|Spencer, Brian; Kim, Changyoun; Gonzalez, Tania et al. (2016) ?-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease. Hum Mol Genet 25:1100-15|
|Valera, E; Monzio Compagnoni, G; Masliah, E (2016) Review: Novel treatment strategies targeting alpha-synuclein in multiple system atrophy as a model of synucleinopathy. Neuropathol Appl Neurobiol 42:95-106|
|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|
|Valera, Elvira; Masliah, Eliezer (2016) Therapeutic approaches in Parkinson's disease and related disorders. J Neurochem 139 Suppl 1:346-352|
|Valera, Elvira; Masliah, Eliezer (2016) Combination therapies: The next logical Step for the treatment of synucleinopathies? Mov Disord 31:225-34|
|Valera, Elvira; Spencer, Brian; Masliah, Eliezer (2016) Immunotherapeutic Approaches Targeting Amyloid-?, ?-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders. Neurotherapeutics 13:179-89|
|Mandler, Markus; Valera, Elvira; Rockenstein, Edward et al. (2015) Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy. Mol Neurodegener 10:10|
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