额颞叶痴呆/肌萎缩侧索硬化症敲入小鼠模型的多模态比较表型分析。

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Disease Models & Mechanisms Pub Date : 2025-08-01 Epub Date: 2025-08-26 DOI:10.1242/dmm.052324
Sevda Boyanova, Gareth Banks, Tatiana V Lipina, Rasneer Sonia Bains, Hamish Forrest, Michelle Stewart, Mireia Carcolé, Carmelo Milioto, Adrian M Isaacs, Sara E Wells, Frances K Wiseman
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引用次数: 0

摘要

肌萎缩性侧索硬化症(ALS)和额颞叶痴呆(FTD)是进行性成人发病的神经退行性疾病,具有重叠的病理和遗传起源。它们是由多种潜在机制引起的,这些机制导致了一系列常见的临床特征。在这里,我们报告了两种ALS/FTD小鼠模型的纵向行为,认知和感觉表型,以确定它们概括了疾病的哪些方面。我们使用敲入模型,在该模型中,C9orf72和TARDBP(编码TDP-43)基因的内源性小鼠同源基因被改变,以模拟ALS/FTD的特定分子方面。我们发现C9orf72GR400/+模型表现出与年龄相关的短期记忆缺陷,亲本基因型影响后代的探索活动。在TardbpQ331K/Q331K模型中,我们发现了体重、脂肪量、运动和大理石掩埋的年龄相关变化。在这两种模型中,我们都没有发现视力或嗅觉习惯缺陷的证据。这些数据为了解这些ALS/FTD小鼠的基因型-表型关系提供了新的见解,可用于未来研究的模型选择和实验设计。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis.

Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis.

Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis.

Multi-modal comparative phenotyping of knock-in mouse models of frontotemporal dementia/amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive adult-onset neurodegenerative diseases with overlapping pathological and genetic origins. They are caused by multiple underlying mechanisms leading to a common collection of clinical features that occur in a spectrum. Here, we report side-by-side longitudinal behavioural, cognitive and sensory phenotyping of two mouse models of ALS/FTD, to determine which aspects of the disease they recapitulate. We used knock-in models, in which the endogenous mouse orthologues of the C9orf72 and TARDBP (encoding TDP-43) genes have been altered to model specific molecular aspects of ALS/FTD. We found that the C9orf72GR400/+ model exhibits age-related deficit in short-term memory and that parental genotype affects exploration activity in offspring. In the TardbpQ331K/Q331K model, we found age-related changes in weight, fat mass, locomotion and marble burying. In both models, we found no evidence of deficits in vision or olfactory habituation-dishabituation. These data provide new insight into genotype-phenotype relationships in these ALS/FTD mice, which can be used to inform model choice and experimental design in future research studies.

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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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