New Olig1 null mice confirm a non-essential role for Olig1 in oligodendrocyte development.
New Olig1 null mice confirm a non-essential role for Olig1 in oligodendrocyte development.
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DOI：
10.1186/1471-2202-15-12
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发表时间：
2014-01-14
期刊：
影响因子：
2.4
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Paes de Faria J;Kessaris N;Andrew P;Richardson WD;Li H
Olig1 和 Olig2 编码密切相关的基本螺旋-环-螺旋转录因子，最初是在神经胶质细胞特异性基因的筛选中发现的。 Olig1 和 Olig2 均在胚胎脊髓和端脑的神经上皮的限制部分中表达，随后在整个生命过程中在少突胶质细胞谱系细胞中表达。在脊髓中，Olig2 在少突胶质细胞和运动神经元的发育中起着至关重要的作用，而这两种细胞类型在 Olig2 缺失突变小鼠中都会丢失。 Olig1 的作用更加神秘。最初报道称，Olig1 缺失小鼠（Olig1 位点带有 Cre-Pgk-Neo 盒）具有轻度发育表型，其特征是少突胶质细胞分化略有延迟。然而，在去除 Pgk-Neo（留下 Olig1-Cre）后对同一细胞系进行的一项后续研究发现，少突胶质细胞产生严重破坏、髓鞘形成失败和产后早期致死。有人提出了一个合理的解释，即原始品系中高表达的 Pgk-Neo 盒可能上调了邻近的 Olig2 基因，补偿了 Olig1 的损失。然而，这尚未经过测试，因此 Olig1 对于少突胶质细胞发育的重要性仍不清楚。我们生成了两个独立的 Olig1 缺失小鼠品系。两个品系均具有轻微的表型，其特点是少突胶质细胞分化和成熟略有延迟，但没有长期影响。此外，我们发现 Olig2 转录本在 Olig1 缺失小鼠中并未上调。我们的研究结果支持最初的结论，即 Olig1 在少突胶质细胞发育中发挥次要且非必需的作用，并且对基于不同来源的 Olig1 缺陷小鼠（可能还有 Olig1-Cre 小鼠）的研究的解释具有影响。
Olig1 and Olig2, encoding closely related basic helix-loop-helix transcription factors, were originally identified in screens for glial-specific genes. Olig1 and Olig2 are both expressed in restricted parts of the neuroepithelium of the embryonic spinal cord and telencephalon and subsequently in oligodendrocyte lineage cells throughout life. In the spinal cord, Olig2 plays a crucial role in the development of oligodendrocytes and motor neurons, and both cell types are lost from Olig2 null mutant mice. The role of Olig1 has been more cryptic. It was initially reported that Olig1 null mice (with a Cre-Pgk-Neo cassette at the Olig1 locus) have a mild developmental phenotype characterized by a slight delay in oligodendrocyte differentiation. However, a subsequent study of the same line following removal of Pgk-Neo (leaving Olig1-Cre) found severe disruption of oligodendrocyte production, myelination failure and early postnatal lethality. A plausible explanation was proposed, that the highly expressed Pgk-Neo cassette in the original line might have up-regulated the neighbouring Olig2 gene, compensating for loss of Olig1. However, this was not tested, so the importance of Olig1 for oligodendrocyte development has remained unclear. We generated two independent lines of Olig1 null mice. Both lines had a mild phenotype featuring slightly delayed oligodendrocyte differentiation and maturation but no long-term effect. In addition, we found that Olig2 transcripts were not up-regulated in our Olig1 null mice. Our findings support the original conclusion that Olig1 plays a minor and non-essential role in oligodendrocyte development and have implications for the interpretation of studies based on Olig1 deficient mice (and perhaps Olig1-Cre mice) from different sources.
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