Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer's disease.
Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer's disease.
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DOI：
10.1002/trc2.12417
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发表时间：
2023-07
影响因子：
4.8
通讯作者：
Silva, Afonso C
中科院分区：
文献类型：
--
作者：
Sukoff Rizzo, Stacey J;Homanics, Gregg;Schaeffer, David J;Schaeffer, Lauren;Park, Jung Eun;Oluoch, Julia;Zhang, Tingting;Haber, Annat;Seyfried, Nicholas T;Paten, Benedict;Greenwood, Anna;Murai, Takeshi;Choi, Sang Ho;Huhe, Hasi;Kofler, Julia;Strick, Peter L;Carter, Gregory W;Silva, Afonso C
我们对引发阿尔茨海默病 (AD) 的机制了解有限，导致缺乏阻止、预防或完全治疗这种疾病的干预措施。我们相信，开发 AD 非人类灵长类动物模型将是克服其他模型系统局限性的重要一步，对于研究 AD 发病和进展的细胞和分子根本原因的灵长类特异性机制至关重要。在国家老龄化研究所的资助下，成立了一个新的联盟，旨在生成、表征和验证狨猴作为 AD 研究模型 (MARMO-AD)。该联盟将使用非侵入性纵向评估，研究携带 AD 遗传风险的基因编辑狨猴模型和野生型基因多样化的衰老狨猴，从出生到其整个生命周期。其中包括表征衰老和 AD 的遗传、分子、功能、行为、认知和病理特征。该联盟使用 CRISPR/Cas9 方法成功地在 C410Y 和 A426P 中产生了携带 PSEN1 突变的可行创始人，并在 C410Y 系中证明了种系传播。这些模型、它们的种系后代和正常衰老的远交狨猴的纵向表征正在进行中。该联盟的所有数据和资源将与更大的 AD 研究界共享。通过建立 AD 狨猴模型，我们将能够研究 AD 发病机制和进展的灵长类特异性细胞和分子根本原因，克服其他模型生物的局限性，并支持未来的转化研究，以加快为患者提供治疗的步伐。
Our limited understanding of the mechanisms that trigger the emergence of Alzheimer's disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that the development of a non‐human primate model of AD will be an essential step toward overcoming limitations of other model systems and is crucial for investigating primate‐specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD. A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets As Research Models of AD (MARMO‐AD). This consortium will study gene‐edited marmoset models carrying genetic risk for AD and wild‐type genetically diverse aging marmosets from birth throughout their lifespan, using non‐invasive longitudinal assessments. These include characterizing the genetic, molecular, functional, behavioral, cognitive, and pathological features of aging and AD. The consortium successfully generated viable founders carrying PSEN1 mutations in C410Y and A426P using CRISPR/Cas9 approaches, with germline transmission demonstrated in the C410Y line. Longitudinal characterization of these models, their germline offspring, and normal aging outbred marmosets is ongoing. All data and resources from this consortium will be shared with the greater AD research community. By establishing marmoset models of AD, we will be able to investigate primate‐specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients.
影响因子：
2.4
作者：
Braun, Katarina;Schultz-Darken, Nancy;Schneider, Mary;Moore, Colleen F.;Emborg, Marina E.
通讯作者：
Emborg, Marina E.