Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington's Disease.

IF 2.1 Q3 NEUROSCIENCES Journal of Huntington's disease Pub Date : 2024-01-01 DOI:10.3233/JHD-231516
Renee R Handley, Suzanne J Reid, Zoe Burch, Jessie C Jacobsen, Tammy Gillis, Kevin Correia, Skye R Rudiger, Clive J McLaughlin, C Simon Bawden, Marcy E MacDonald, Vanessa C Wheeler, Russell G Snell
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Abstract

Somatic instability of the huntingtin (HTT) CAG repeat mutation modifies age-at-onset of Huntington's disease (HD). Understanding the mechanism and pathogenic consequences of instability may reveal therapeutic targets. Using small-pool PCR we analyzed CAG instability in the OVT73 sheep model which expresses a full-length human cDNA HTT transgene. Analyses of five- and ten-year old sheep revealed the transgene (CAG)69 repeat was remarkably stable in liver, striatum, and other brain tissues. As OVT73 sheep at ten years old have minimal cell death and behavioral changes, our findings support instability of the HTT expanded-CAG repeat as being required for the progression of HD.

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亨廷顿氏症转基因绵羊模型中体细胞 CAG 重复序列的稳定性。
亨廷顿蛋白(HTT)CAG重复突变的体细胞不稳定性改变了亨廷顿病(HD)的发病年龄。了解不稳定性的机制和致病后果可能会发现治疗目标。我们利用小池 PCR 分析了表达全长人类 cDNA HTT 转基因的 OVT73 羊模型中的 CAG 不稳定性。对 5 岁和 10 岁绵羊的分析表明,转基因 (CAG)69 重复序列在肝脏、纹状体和其他脑组织中非常稳定。由于十岁的 OVT73 羊细胞死亡和行为变化极小,我们的研究结果支持 HTT 扩增-CAG 重复的不稳定性是 HD 进展的必要条件。
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来源期刊
CiteScore
4.80
自引率
9.70%
发文量
60
期刊最新文献
Changes in 24(S)-Hydroxycholesterol Are Associated with Cognitive Performance in Early Huntington's Disease: Data from the TRACK and ENROLL HD Cohorts. Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington's Disease. Mono- and Biallelic Inactivation of Huntingtin Gene in Patient-Specific Induced Pluripotent Stem Cells Reveal HTT Roles in Striatal Development and Neuronal Functions. Alterations in Cerebrospinal Fluid Urea Occur in Late Manifest Huntington's Disease. Characterizing Heart Rate Variability Response to Maximal Exercise Testing in People with Huntington's Disease.
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