دورية أكاديمية
Enhancing face validity of mouse models of Alzheimer's disease with natural genetic variation.
| العنوان: | Enhancing face validity of mouse models of Alzheimer's disease with natural genetic variation. |
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| المؤلفون: | Onos, Kristen D, Uyar, Asli, Keezer, Kelly J, Jackson, Harriet M, Preuss, Christoph, Acklin, Casey J, O'Rourke, Rita, Buchanan, Rebecca, Cossette, Travis L, Sukoff Rizzo, Stacey J, Soto Reyes, Ileana, Carter, Gregory W, Howell, Gareth R |
| المصدر: | Faculty Scholarship for the College of Science & Mathematics |
| بيانات النشر: | Rowan Digital Works |
| سنة النشر: | 2019 |
| المجموعة: | Rowan University: Rowan Digital Works |
| مصطلحات موضوعية: | Genetics and Genomics, Medicine and Health Sciences |
| الوصف: | Classical laboratory strains show limited genetic diversity and do not harness natural genetic variation. Mouse models relevant to Alzheimer's disease (AD) have largely been developed using these classical laboratory strains, such as C57BL/6J (B6), and this has likely contributed to the failure of translation of findings from mice to the clinic. Therefore, here we test the potential for natural genetic variation to enhance the translatability of AD mouse models. Two widely used AD-relevant transgenes, APPswe and PS1de9 (APP/PS1), were backcrossed from B6 to three wild-derived strains CAST/EiJ, WSB/EiJ, PWK/PhJ, representative of three Mus musculus subspecies. These new AD strains were characterized using metabolic, functional, neuropathological and transcriptional assays. Strain-, sex- and genotype-specific differences were observed in cognitive ability, neurodegeneration, plaque load, cerebrovascular health and cerebral amyloid angiopathy. Analyses of brain transcriptional data showed strain was the greatest driver of variation. We identified significant variation in myeloid cell numbers in wild type mice of different strains as well as significant differences in plaque-associated myeloid responses in APP/PS1 mice between the strains. Collectively, these data support the use of wild-derived strains to better model the complexity of human AD. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://rdw.rowan.edu/csm_facpub/146Test; https://rdw.rowan.edu/context/csm_facpub/article/1145/viewcontent/Soto_Reyes2019_PLoSGenetics_Enhancing.pdfTest |
| DOI: | 10.1371/journal.pgen.1008155 |
| الإتاحة: | https://doi.org/10.1371/journal.pgen.1008155Test https://rdw.rowan.edu/csm_facpub/146Test https://rdw.rowan.edu/context/csm_facpub/article/1145/viewcontent/Soto_Reyes2019_PLoSGenetics_Enhancing.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.B3490AD0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pgen.1008155 |
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