Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Mouse Genome Engineering Core Facility, University of Nebraska Medical Center, Omaha, NE 68198.
eNeuro. 2021 Feb 1;8(1). doi: 10.1523/ENEURO.0221-20.2021. Print 2021 Jan-Feb.
Motor neurons (MNs) innervating the digit muscles of the intrinsic hand (IH) and intrinsic foot (IF) control fine motor movements. The ability to reproducibly label specifically IH and IF MNs in mice would be a beneficial tool for studies focused on fine motor control. To this end, we find that a CRE knock-in mouse line of , a developmentally expressed basic helix-loop-helix (bHLH) transcription factor, reliably expresses CRE-dependent reporter genes in ∼60% of the IH and IF MNs. We determine that CRE-dependent expression in IH and IF MNs is ectopic because an mouse line driving FLPo recombinase does not label these MNs although other -lineage neurons in the intermediate spinal cord are reliably identified. Furthermore, the CRE-dependent reporter expression is enriched in the IH and IF MN pools with much sparser labeling of other limb-innervating MN pools such as the tibialis anterior (TA), gastrocnemius (GS), quadricep (Q), and adductor (Ad). Lastly, we find that ectopic reporter expression begins postnatally and labels a mixture of α and γ-MNs. Altogether, the CRE knock-in mouse strain might be a useful tool to explore the function and connectivity of MNs involved in fine motor control when combined with other genetic or viral strategies that can restrict labeling specifically to the IH and IF MNs. Accordingly, we provide an example of sparse labeling of IH and IF MNs using an intersectional genetic approach.
运动神经元（MNs）支配着内在手（IH）和内在脚（IF）的手指肌肉，控制着精细的运动。能够在小鼠中可靠地标记特定的 IH 和 IF MNs，将是研究精细运动控制的有益工具。为此，我们发现一种发育表达的基本螺旋-环-螺旋（bHLH）转录因子 CRE 敲入小鼠系，在大约 60%的 IH 和 IF MNs 中可靠地表达 CRE 依赖性报告基因。我们确定 IH 和 IF MNs 中的 CRE 依赖性表达是异位的，因为驱动 FLPo 重组酶的 小鼠系不能标记这些 MNs，尽管中间脊髓中的其他 -谱系神经元可以可靠地识别。此外，CRE 依赖性报告基因的表达在 IH 和 IF MN 池中富集，而其他支配肢体的 MN 池（如胫骨前肌（TA）、腓肠肌（GS）、四头肌（Q）和内收肌（Ad））的标记则稀疏得多。最后，我们发现异位报告基因的表达始于出生后，并标记了α和γ-MNs 的混合物。总的来说，当与其他可以将标记物特异性限制在 IH 和 IF MNs 的遗传或病毒策略结合使用时， CRE 敲入小鼠品系可能是探索参与精细运动控制的 MNs 的功能和连接性的有用工具。因此，我们提供了一种使用交叉遗传方法稀疏标记 IH 和 IF MNs 的示例。
