Tool Mice 工具小鼠
In neuroscience research, fluorescent reporter systems serve as essential tools for dissecting neural connectivity and tracing cell fate. In 2024, a team led by Kiryl D. Piatkevich at Westlake University developed mBaojin, a high-brightness and highly photostable green fluorescent protein derived from StayGold. In 2025, the group led by Zhifei Fu at Fujian Medical University engineered mYonghong, an ultra-stable monomeric red fluorescent protein exhibiting exceptional chemical, thermal, and photostability. In close collaboration with these teams, the Zhao Hu laboratory at the Chinese Institute for Brain Research (CIBR) leveraged these advanced fluorescent protein tools to develop a series of Ci reporter mouse lines.
These next-generation mouse models are fully comparable to conventional Rosa26-GFP/tdTomato reporter lines in standard applications, while demonstrating pronounced advantages under demanding experimental conditions such as tissue clearing. They enable advanced applications that are challenging for traditional reporters, including tissue clearing, super-resolution imaging, correlative light and electron microscopy (CLEM), and organelle-specific targeting. Collectively, these models provide powerful tools for deeper and higher-resolution three-dimensional tissue imaging, particularly for the fine-scale dissection of neural circuits.
在神经科学研究中,荧光报告系统是解析神经连接与追踪细胞命运的核心工具。2024年,西湖大学Kiryl D. Piatkevich团队开发了源自StayGold的高亮度、高光稳定性绿色荧光蛋白mBaojin;2025年,福建医科大学付志飞团队开发了超稳定单体红色荧光蛋白mYonghong,在化学稳定性、热稳定性和光稳定性方面均表现出卓越性能。北京脑科学与类脑研究所(Chinese Institute for Brain Research, CIBR)赵瑚团队与上述团队密切合作,基于这些先进荧光蛋白工具构建并开发了一系列Ci报告基因小鼠。
该系列新型小鼠模型在基础研究应用中可全面对标Rosa26-GFP/tdTomato工具鼠,尤其在耐受组织透明化等高强度处理流程方面展现出显著优势,可胜任传统工具难以完成的组织透明化、超分辨成像、CLEM及细胞器靶向等前沿研究工作。该模型体系为实现更深层次、更高分辨率的三维组织成像,特别是在神经环路的精细结构解析方面,提供了强有力的技术支撑。
Common Name | Strain # | Target Gene | Type of Induction | Fluorescent Proteins | Reference | Characteristic |
|---|---|---|---|---|---|---|
| Ci16 | GAP4026 | H11 | Cre | mYongHong (Red) | Haiyan et al., 2025 | Cre驱动的广谱细胞标记,常规胞 体/树突成像,CLEM前光镜定位 |
| Ci1 | GAP4035 | H11 | Cre | mScarlet (Red) | Manyu et al., 2025 | 特异性表达于胞浆 |
| Ci13 | GAP4036 | H11 | Cre | mYongHong (Red) | Haiyan et al., 2025 | 特异性表达于内质网 |
| Ci14 | GAP4037 | H11 | Cre | mYongHong (Red) | Haiyan et al., 2025 | 特异性表达于细胞核内 |
| Ci15 | GAP4038 | H11 | Cre | mScarlet (Red) | 特异性表达于细胞核内 | |
| Ci17 | GAP4039 | H11 | Cre | mYongHong (Red) | Haiyan et al., 2025 | CLEM适配:Cre驱动的神经投射 追踪+电镜超微分析;iDISCO全脑 3D透明化成像 |
| Ci18 | GAP4040 | H11 | Cre | mBaojin (Green) | Hanbin et al., 2024 | Cre驱动的广谱细胞标记,绿色荧光 通道常规光镜成像,短期活体追踪 |
| Ci19 | GAP4041 | H11 | Cre | mBaojin (Green) | Hanbin et al., 2024 | Cre驱动的绿色荧光通道神经投射 追踪,膨胀显微镜超高分辨率成像 |
| Ci20 | GAP4042 | H11 | Cre | mScarlet3 (Red) | 红色荧光高亮度报告基因,可更好 地标记神经轴突投射,适用于各类 组织透明化成像及膨胀显微镜,不 适用于CLEM | |
| Ci22 | GAP4043 | H11 | Cre | mKate2 (Red) | 活体成像,突触标记 | |
| Ci23 | GAP4044 | H11 | Cre | mTagBFP2 (Blue) | 特异性表达于细胞核 | |
| Ci24 | GAP4045 | H11 | Cre,Dre | mYongHong (Red) | Haiyan et al., 2025 | CLEM适配:双基因调控的细胞类 型特异性标记+电镜超微分析,精 准长距离轴突追踪 |
| Ci25 | GAP4046 | H11 | Cre,Dre | mScarlet3 (Red) | 双酶调控,红色荧光高亮度报告基 因,可更好地标记神经轴突投射, 适用于各类组织透明化成像及膨胀 显微镜,不适用于CLEM。 | |
| Ci26 | GAP4047 | H11 | Cre,Flp | mYongHong (Red) | Haiyan et al., 2025 | CLEM适配:双基因调控的细胞类 型特异性标记,红色荧光轴突成像+ 电镜超微分析 |
| Ci27 | GAP4048 | H11 | Cre,Flp | mBaojin (Green) | Hanbin et al., 2024 | 双基因调控的细胞类型特异性标记, 绿色荧光轴突成像/活体/ 膨胀显 微镜成像 |
| Ci30 | GAP4049 | H11 | Dre | mScarlet3 (Red) | 红色荧光高亮度报告基因,可更好 地标记神经轴突投射,适用于各类 组织透明化成像及膨胀显微镜,不 适用于 CLEM。 | |
| Ci31 | GAP4050 | H11 | Dre | mBaojing (Green) | Hanbin et al., 2024 | Dre驱动的特异性神经投射追踪,绿 色荧光通道常规光镜/活体成像 |
| Ci32 | GAP4051 | H11 | Flp | mYongHong (Red) | Haiyan et al., 2025 | CLEM适配:Flp驱动的特异性神经 投射追踪+电镜超微分析 |
| Ci33 | GAP4052 | H11 | Flp | mBaojin (Green) | Hanbin et al., 2024 | Flp驱动的特异性神经投射追踪,绿 色荧光通道活体/膨胀显微镜成像 |
| Ci34 | GAP4053 | H11 | Cre,Flp | mYongHong (Red) mBaojin (Green) | Haiyan et al., 2025 Hanbin et al., 2024 | 双基因调控下的双色细胞标记,区分 Cre+/Flp+细胞亚群(纯光镜实验) |
| Ci35 | GAP4054 | H11 | Cre,Dre | mYongHong (Red) mBaojin (Green) | Haiyan et al., 2025 Hanbin et al., 2024 | 双基因调控下的双色细胞标记,Cre/ Dre驱动的细胞亚群区分(纯光镜实验) |
| Ci37 | GAP4056 | H11 | Cre | mYongHong (Red) | Haiyan et al., 2025 | CLEM适配:神经元特异性标记+电镜 超微分析,Cre驱动的神经元投射追踪 |
Common Name | Strain # | Target Gene | Recombinase | Require Induction | Reference | Characteristic |
|---|---|---|---|---|---|---|
| Vglut2-Cre | GAP1008 | Vglut2 | Cre | 否 | 谷氨酸能神经元 | |
| Vglut2-iCreERT2 | GAP1180 | Vglut2 | CreERT2 | 是 | 谷氨酸能神经元 | |
| Vglut2-Flp | GAP1119 | Vglut2 | Flpo | 否 | 谷氨酸能神经元 | |
| Vglut3-Cre | GAP1136 | Vglut3 | Cre | 否 | 谷氨酸能神经元 | |
| Pv-Cre | GAP1002 | Pvalb | Cre | 否 | Minghui et al., 2021 | GABA能神经元 小白蛋白的神经元 |
| Pv-Flp | GAP1116 | Pvalb | Flpo | 否 | GABA能神经元 小白蛋白的神经元 | |
| Sst-Cre | GAP1003 | Sst | Cre | 否 | GABA能神经元 生长抑素阳性神经元 | |
| Sst-Flp | GAP1117 | Sst | Flpo | 否 | GABA能神经元 生长抑素阳性神经元 | |
| Vgat-Cre | GAP1041 | Cre | 否 | GABA 能神经元 | ||
| Vgat-Flp | GAP1120 | Vgat | Flpo | 否 | GABA 能神经元 | |
| Gad2-Cre | GAP1011 | Gad2 | Cre | 否 | GABA 能神经元 | |
| Gad2-Flp | GAP1118 | Gad2 | Flpo | 否 | GABA 能神经元 | |
| Chat-Cre | GAP1040 | Chat | Cre | 否 | 胆碱能神经元 | |
| Chat-CreERT2 | GAP1086 | Chat | CreERT2 | 是 | 胆碱能神经元 | |
| Dat-Cre | GAP1037 | Dat | Cre | 否 | 多巴胺能神经元 | |
| Th-Cre | GAP1121 | Th | Cre | 否 | 多巴胺能神经元 | |
| Th-CreERT2 | GAP1125 | Th | CreERT2 | 是 | 多巴胺能神经元 | |
| Drd1-Cre | GAP1135 | Drd1 | Cre | 否 | 多巴胺能神经元 | |
| Drd2-Cre | GAP1059 | Drd2 | Cre | 否 | 多巴胺能神经元 | |
| Dbh-Cre | GAP1134 | Dbh | Cre | 否 | 去甲肾上腺素能神经元 | |
| Dbh-Flp | GAP1128 | Flpo | 否 | 去甲肾上腺素能神经元 | ||
| Sert-Cre | GAP1133 | Sert | Cre | 否 | 5-羟色胺能神经元 | |
| Pet1-Cre | GAP1039 | Pet1 | Cre | 否 | 5-羟色胺能神经元 | |
| Crh-Cre | GAP1013 | Crh | Cre | 否 | 促肾上腺皮质激素释放 激素阳性神经元 | |
| Calca-Cre | GAP1127 | Calca | Cre | 否 | 研究与食欲相关的神经回路 | |
| Oxt-Cre | GAP1131 | Oxt | Cre | 否 | 催产素神经元 | |
| Fos-CreERT2 | GAP1031 | Fos | CreERT2 | 是 | ||
| Cx3cr1-CreERT2 | GAP1012 | Cx3cr1 | CreERT2 | 是 | 小胶质细胞 | |
| Tmem119-CreERT2 | GAP1068 | Tmeme119 | CreERT2 | 是 | 星形胶质细胞 | |
| Tac1-Cre | GAP1026 | Tac1 | Cre | 否 | P物质阳性神经元 | |
| Tac1-iCreERT2 | GAP1174 | Tac1 | CreERT2 | 是 | P物质阳性神经元 | |
| Penk-Cre | GAP1030 | Penk | Cre | 否 | 脑啡肽阳性神经元 | |
| Penk-iCreERT2 | GAP1155 | Penk | CreERT2 | 是 | 脑啡肽阳性神经元 |
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