Centre de Recherche du CHU de Québec-Université Laval, Québec, QC, Canada; Département de Médecine Moléculaire, Université Laval Québec, Québec, QC, Canada.
Centre de Recherche du CHU de Québec-Université Laval, Québec, QC, Canada; Département de Médecine Moléculaire, Université Laval Québec, Québec, QC, Canada.
Behav Brain Res. 2023 Jan 5;436:114107. doi: 10.1016/j.bbr.2022.114107. Epub 2022 Sep 8.
Friedreich Ataxia (FRDA) is a genetic disease caused by an expended GAA repeat in the FXN gene leading to a reduction in frataxin protein production. Frataxin is an essential protein involved in mitochondrial iron-sulfur-cluster formation, its absence affecting numerous cellular rections. In patients, the disease leads to a progressive neuromuscular degeneration and, most of the time, death from heart failure. In order to determine if a treatment is effective or not, it is essential to have the mouse model, which best reflects all of the characteristics of this disease. Many groups were working on the creation of mouse models by decreasing the mouse frataxin or knocking it out, by introducing a transgene with a human frataxin with long GAA repeat. Most of the mouse models are limited to one problem, either neurologic or cardiac symptoms, and, for those who have both, generally these symptoms are too severe and mice have a very short life span, which does not reflect the human disease's progression. Jackson Laboratories Inc. developed a new mouse model that has 800 GAA repeats. We demonstrate here that these mice accurately reflect the human disease with a progressive neuromuscular degeneration highlighted by the two beam tests and the beginning of heart hypertrophy at 26 weeks. YG8-800 mice are thus currently a promising mouse model for FRDA.
弗里德赖希共济失调（FRDA）是一种由 FXN 基因中 GAA 重复扩展引起的遗传性疾病，导致 frataxin 蛋白产量减少。Frataxin 是一种参与线粒体铁硫簇形成的必需蛋白，其缺失会影响许多细胞反应。在患者中，该疾病导致进行性神经肌肉退化，并且大多数情况下，心力衰竭导致死亡。为了确定治疗是否有效，拥有最能反映该疾病所有特征的小鼠模型至关重要。许多研究小组通过减少小鼠 frataxin 或敲除它，或通过引入带有长 GAA 重复的人类 frataxin 的转基因，来创建小鼠模型。大多数小鼠模型仅限于一个问题，即神经或心脏症状，对于那些同时具有这两种症状的模型，通常这些症状过于严重，并且小鼠的寿命非常短，这不能反映人类疾病的进展。杰克逊实验室公司开发了一种具有 800 个 GAA 重复的新型小鼠模型。我们在这里证明，这些小鼠通过双光束测试突出显示进行性神经肌肉退化，并在 26 周时开始出现心脏肥大，准确地反映了人类疾病。因此，YG8-800 小鼠目前是 FRDA 的一种有前途的小鼠模型。
