Division of Cellular & Molecular Neurobiology, Zoological Institute, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany.
Int J Mol Sci. 2021 Oct 21;22(21):11348. doi: 10.3390/ijms222111348.
Zebrafish have come into focus to model cerebellar diseases such as spinocerebellar ataxias (SCAs), which is caused by an expansion of translated CAG repeats in several unrelated genes. In spinocerebellar ataxia type 1 (SCA1), gain-of-function in the mutant ATXN1 contributes to SCA1's neuropathy. Human ATXN1 and its paralog ATXN1L are chromatin-binding factors, act as transcriptional repressors, and have similar expression patterns. However, little is known about genes in zebrafish. Recently, two family members, and , were identified as duplicate orthologs of , as was a, the ortholog of . In this study, we analyzed the phylogenetic relationship of the family members in zebrafish, compared their genetic structures, and verified the predicted transcripts by both RT-PCR and whole-mount in situ hybridization. All three genes, , , and , show overlapping, but also distinct, expression domains during embryonic and larval development. While and display similar spatiotemporal embryonic expression, expression is initiated during the onset of brain development and is predominantly expressed in the cerebellum throughout zebrafish development. These results provide new insights into genes and their expression patterns in zebrafish during embryonic and late-larval development and may contribute importantly to future experiments in disease modeling of SCAs.
斑马鱼已成为研究小脑疾病（如脊髓小脑共济失调症，SCA）模型的焦点，SCA 是由几个不相关基因中的翻译 CAG 重复序列扩展引起的。在脊髓小脑共济失调症 1 型（SCA1）中，突变 ATXN1 的功能获得导致 SCA1 的神经病变。人类 ATXN1 和其同源物 ATXN1L 是染色质结合因子，作为转录抑制剂发挥作用，并且具有相似的表达模式。然而，对于斑马鱼中的这些基因知之甚少。最近，两个家族成员 和 被鉴定为 的重复直系同源物，而 是 的直系同源物。在这项研究中，我们分析了斑马鱼中 家族成员的系统发育关系，比较了它们的遗传结构，并通过 RT-PCR 和整体原位杂交验证了预测的转录本。所有三个基因 、 和 在胚胎和幼虫发育过程中都表现出重叠但又不同的表达区域。虽然 和 在胚胎期具有相似的时空表达，但 的表达在脑发育开始时启动，并在整个斑马鱼发育过程中主要在小脑表达。这些结果为 基因及其在斑马鱼胚胎和晚期幼虫发育过程中的表达模式提供了新的见解，并可能对 SCA 疾病建模的未来实验做出重要贡献。
