دورية أكاديمية

Enhancing face validity of mouse models of Alzheimer's disease with natural genetic variation.

التفاصيل البيبلوغرافية
العنوان: Enhancing face validity of mouse models of Alzheimer's disease with natural genetic variation.
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
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