Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome.
Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome.
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DOI：
10.1038/s41398-022-02206-3
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发表时间：
2022-10-03
影响因子：
6.8
通讯作者：
Sidorov, Michael S.
中科院分区：
文献类型：
--
作者：
Tanas, Joseph K.;Kerr, Devante D.;Wang, Li;Rai, Anika;Wallaard, Ilse;Elgersma, Ype;Sidorov, Michael S.
Angelman综合征（AS）是一种由UBE 3A基因母源拷贝表达缺失引起的神经发育障碍。AS患者具有多方面的行为表型，包括运动功能缺陷、癫痫、认知障碍、睡眠异常以及其他合并症。有效地模拟这种行为特征并测量行为改善对于正在进行的和未来的临床试验的成功至关重要。基础研究已经在AS小鼠模型中定义了一系列行为表型。然而，没有一个单一的行为测试能够完全捕捉到小鼠或儿童AS的复杂性质。我们进行了多维分析（主成分分析+k均值聚类），以量化AS模型小鼠（n = 148）和野生型同窝小鼠（n = 138）在8个行为领域的表现。该方法基于小鼠的行为特征以约95%的准确度正确预测小鼠的基因型，并且在合理的样本量（n =约12-15）下保持有效。多维分析使用不同的行为输入组合是有效的，并且能够检测AS模型小鼠中作为治疗的函数的行为改善。总体而言，多维行为分析提供了一种评估AS临床前治疗有效性的工具。行为的多维分析也可以应用于相关神经发育障碍的啮齿动物模型，并且对于个体行为测试不如AS可靠的疾病可能特别有价值。
Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have a multifaceted behavioral phenotype consisting of deficits in motor function, epilepsy, cognitive impairment, sleep abnormalities, as well as other comorbidities. Effectively modeling this behavioral profile and measuring behavioral improvement will be crucial for the success of ongoing and future clinical trials. Foundational studies have defined an array of behavioral phenotypes in the AS mouse model. However, no single behavioral test is able to fully capture the complex nature of AS—in mice, or in children. We performed multidimensional analysis (principal component analysis + k-means clustering) to quantify the performance of AS model mice (n = 148) and wild-type littermates (n = 138) across eight behavioral domains. This approach correctly predicted the genotype of mice based on their behavioral profile with ~95% accuracy, and remained effective with reasonable sample sizes (n = ~12–15). Multidimensional analysis was effective using different combinations of behavioral inputs and was able to detect behavioral improvement as a function of treatment in AS model mice. Overall, multidimensional behavioral analysis provides a tool for evaluating the effectiveness of preclinical treatments for AS. Multidimensional analysis of behavior may also be applied to rodent models of related neurodevelopmental disorders, and may be particularly valuable for disorders where individual behavioral tests are less reliable than in AS.
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双ISOOFORM HUBE3A基因转移改善了Angelman综合征模型小鼠的行为和癫痫发作结果。
影响因子：
8
作者：
Judson MC;Shyng C;Simon JM;Davis CR;Punt AM;Salmon MT;Miller NW;Ritola KD;Elgersma Y;Amaral DG;Gray SJ;Philpot BD
通讯作者：
Philpot BD
影响因子：
11
作者：
Keute M;Miller MT;Krishnan ML;Sadhwani A;Chamberlain S;Thibert RL;Tan WH;Bird LM;Hipp JF
通讯作者：
Hipp JF
影响因子：
4.9
作者：
Delling JP;Boeckers TM
通讯作者：
Boeckers TM
影响因子：
6.8
作者：
Heinz DE;Schöttle VA;Nemcova P;Binder FP;Ebert T;Domschke K;Wotjak CT
通讯作者：
Wotjak CT
影响因子：
64.8
作者：
Huang, Hsien-Sung;Allen, John A.;Mabb, Angela M.;King, Ian F.;Miriyala, Jayalakshmi;Taylor-Blake, Bonnie;Sciaky, Noah;Dutton, J. Walter, Jr.;Lee, Hyeong-Min;Chen, Xin;Jin, Jian;Bridges, Arlene S.;Zylka, Mark J.;Roth, Bryan L.;Philpot, Benjamin D.
通讯作者：
Philpot, Benjamin D.