Core D Animals The Animal Core is central to the Program Project, performing bioassay experiments for Projects 1, 2, 3 and 4, and supplying tissues to the Neuropathology core (Core C), and tail biopsies to the Science core (Core B) for screening. The Animal Core will provide the following services: the highest quality animal and veterinary care; breeding of transgenic and knockout mice; experimental inoculations, and neurologic scoring of animals; bioluminescence imaging; behavioral assessments; tissue collection and storage; transportation of animals and tissues between the animal facility and the laboratory; microinjection of DNA constructs to generate new transgenic lines; and cryopreservation of new transgenic mouse lines. The demonstration that inoculation of A and tau aggregates can initiate self-propagation in the appropriate mouse model is a clear analogy to the prion diseases. However a major limitation of the A and tau inoculation models is that the mice don't show any overt clinical signs, and the only way of determining the degree of disease progression is to remove the brain for biochemical and neuropathological analysis. Our pioneering work in the field of bioluminescence imaging (BLI) and near infrared (NIR) fluorescence imaing has allowed us to address this issue and monitor disease progression in vivo. We have developed transgenic mouse models incorporating a luciferase reporter, enabling monitoring by BLI, for propagation of the prion protein (PrP) and A, and NIR fluorescent ligands that bind to tau. These provide a suite of tools to determine the biological relevance of protein and peptide aggregates formed in the Projects of this grant.
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| Condello, Carlo; Lemmin, Thomas; Stöhr, Jan et al. (2018) Structural heterogeneity and intersubject variability of A? in familial and sporadic Alzheimer's disease. Proc Natl Acad Sci U S A 115:E782-E791 |
| Woerman, Amanda L; Kazmi, Sabeen A; Patel, Smita et al. (2018) MSA prions exhibit remarkable stability and resistance to inactivation. Acta Neuropathol 135:49-63 |
| Yang, Bing; Wu, Haifan; Schnier, Paul D et al. (2018) Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry. Proc Natl Acad Sci U S A 115:11162-11167 |
| Irimata, Katherine E; Dugger, Brittany N; Wilson, Jeffrey R (2018) Impact of the Presence of Select Cardiovascular Risk Factors on Cognitive Changes among Dementia Subtypes. Curr Alzheimer Res 15:1032-1044 |
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| Woerman, Amanda L; Watts, Joel C; Aoyagi, Atsushi et al. (2018) ?-Synuclein: Multiple System Atrophy Prions. Cold Spring Harb Perspect Med 8: |
| Woerman, Amanda L; Kazmi, Sabeen A; Patel, Smita et al. (2018) Familial Parkinson's point mutation abolishes multiple system atrophy prion replication. Proc Natl Acad Sci U S A 115:409-414 |
| Johnson, Noah R; Condello, Carlo; Guan, Shenheng et al. (2017) Evidence for sortilin modulating regional accumulation of human tau prions in transgenic mice. Proc Natl Acad Sci U S A 114:E11029-E11036 |
| Gerkin, Richard C; Adler, Charles H; Hentz, Joseph G et al. (2017) Improved diagnosis of Parkinson's disease from a detailed olfactory phenotype. Ann Clin Transl Neurol 4:714-721 |
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