A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality
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Abstract
Modern genetic approaches are powerful in providing access to diverse cell types in the brain and facilitating the study of their function. Here, we report a large set of driver and reporter transgenic mouse lines, including 23 new driver lines targeting a variety of cortical and subcortical cell populations and 26 new reporter lines expressing an array of molecular tools. In particular, we describe the TIGRE2.0 transgenic platform and introduce Cre-dependent reporter lines that enable optical physiology, optogenetics, and sparse labeling of genetically defined cell populations. TIGRE2.0 reporters broke the barrier in transgene expression level of single-copy targeted-insertion transgenesis in a wide range of neuronal types, along with additional advantage of a simplified breeding strategy compared to our first-generation TIGRE lines. These novel transgenic lines greatly expand the repertoire of high-precision genetic tools available to effectively identify, monitor, and manipulate distinct cell types in the mouse brain.
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Module 30 is more specific to the hypothalamus than other regions of the BS.
“Based on the locations from the Allen Brain Atlas51 (Figure S13A), we find module 30 to be more specific to the hypothalamus than other regions of the BS (Figure S13B).”
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The authors used many transgenic mouse lines to cover excitatory and inhibitory classes across cortical layers, target rare populations, and connect with other approaches like transcriptomic characterization.
“A diverse set of transgenic mouse lines14–18 were used to ensure broad coverage of excitatory and inhibitory classes across all cortical layers, to enable selective targeting of rare cell populations, and to link our study with other experimental approaches, such as transcriptomic characterization19.”
From Classification of electrophysiological and morphological neuron types in the mouse visual cortex (2019) · cites this paper as [18]
Molecular classification of cell types enables genetic access to specific cell types using transgenic mice and enhancer-based viral vectors.
“Finally, molecular classification of cell types enables genetic access to specific cell types using transgenic mice25–27 and, more recently, enhancer-based viral vectors28–32.”
From A multimodal cell census and atlas of the mammalian primary motor cortex (2021) · cites this paper as [26]
E2 driving synaptophysin-tdTomato restricted reporter expression presynaptically to PV cINs, with terminals peri-somatically located onto pyramidal neurons.
“When E2 was used to drive a synaptophysin-tdTomato fusion gene36, reporter expression was restricted pre-synaptically to PV cINs, with terminals peri-somatically located onto pyramidal neurons”
From Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans (2020) · cites this paper as [36]
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Reassessing the Role of Histaminergic Tuberomammillary Neurons in Arousal Control
Venner, A., Mochizuki, T., De Luca, R., Anaclet, C., Scammell, T. E., Saper, C. B., Arrigoni, E., & Fuller, P. M. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.1032-19.2019 · Cited by 70 · see citing works
Peng, H., Xie, P., Liu, L., Kuang, X., Wang, Y., Qu, L., Gong, H., Jiang, S., Li, A., Ruan, Z., et al. (2019) · doi:10.1101/675280 · Cited by 47 · see citing works
Self-citationCorticothalamic pathways from layer 5: emerging roles in computation and pathology
Mease, R. A., & Gonzalez, A. J. (2021) · Frontiers in Neural Circuits · doi:10.3389/fncir.2021.730211 · Cited by 36 · see citing works
Littman, R., Cheng, M., Wang, N., Peng, C., & Yang, X. (2023) · iScience · doi:10.1016/j.isci.2023.107124 · Cited by 35 · see citing works
Recording and manipulation of the maternal oxytocin neural activities in mice
Yukinaga, H., Hagihara, M., Tsujimoto, K., Chiang, H.-L., Kato, S., Kobayashi, K., & Miyamichi, K. (2022) · Current Biology · doi:10.1016/j.cub.2022.06.083 · Cited by 33 · see citing works
Graybuck (2019) · doi:10.1101/525014 · Cited by 31 · see citing works
New light on cortical neuropeptides and synaptic network plasticity
Smith, S. J., Hawrylycz, M., Rossier, J., & Sümbül, U. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.04.002 · Cited by 26 · see citing works
Intersectional mapping of multi-transmitter neurons and other cell types in the brain
Xu, J., Jo, A., DeVries, R. P., Deniz, S., Cherian, S., Sunmola, I., Song, X., Marshall, J. J., Gruner, K. A., Daigle, T. L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111036 · Cited by 27 · see citing works
Self-citationMatho, K. S., Huilgol, D., Galbavy, W., He, M., Kim, G., An, X., Lu, J., Wu, P., Di Bella, D. J., Shetty, A. S., et al. (2020) · doi:10.1101/2020.04.22.054064 · Cited by 20 · see citing works
Self-citationLong-term Recordings of Arcuate Nucleus Kisspeptin Neurons Across the Mouse Estrous Cycle
Vas, S., Wall, E., Zhou, Z., Kalmar, L., Han, S. Y., & Herbison, A. E. (2024) · Endocrinology · doi:10.1210/endocr/bqae009 · Cited by 14 · see citing works
Brainstem noradrenergic modulation of the kisspeptin neuron GnRH pulse generator in mice
Vas, S., Morris, P. G., Gul, Z., Ruiz-Cruz, M., Han, S. Y., & Herbison, A. E. (2025) · Nature Communications · doi:10.1038/s41467-025-60837-8 · Cited by 7 · see citing works
“D Cre-dependent GCaMP6s line (JAX stock #031562) 61 .”
- Authors
- Daigle, T. L., Madisen, L., Hage, T. A., Valley, M. T., Knoblich, U., Larsen, R. S., Takeno, M. M., Huang, L., Gu, H., Larsen, R., Mills, M., Bosma-Moody, A., Siverts, L. A., Walker, M., Graybuck, L. T., Yao, Z., Fong, O., Nguyen, T. N., Garren, E., Lenz, G. H., Chavarha, M., Pendergraft, J., Harrington, J., Hirokawa, K. E., Harris, J. A., Nicovich, P. R., McGraw, M. J., Ollerenshaw, D. R., Smith, K. A., Baker, C. A., Ting, J. T., Sunkin, S. M., Lecoq, J., Lin, M. Z., Boyden, E. S., Murphy, G. J., da Costa, N. M., Waters, J., Li, L., Tasic, B., & Zeng, H.
- Affiliations
- Allen Institute for Brain Science (US)
- Stanford Medicine (US)
- McGovern Institute for Brain Research (US)
- Corresponding author
- Zeng, Hongkui
- ORCID
- Daigle, Tanya L.
- Hage, Travis A.
- Valley, Matthew T.
- Knoblich, Ulf
- Larsen, Rylan S.
- Takeno, Marc M.
- Larsen, Rachael
- Siverts, La’ Akea
- Walker, Miranda
- Graybuck, Lucas T.
- Yao, Zizhen
- Fong, Olivia
- Nguyen, Thuc Nghi
- Lenz, Garreck H.
- Chavarha, Mariya
- Pendergraft, Julie
- Hirokawa, Karla E.
- Harris, Julie A.
- Nicovich, Philip R.
- Ollerenshaw, Douglas R.
- Smith, Kimberly A.
- Baker, Christopher A.
- Ting, Jonathan T.
- Sunkin, Susan M.
- Lecoq, Jérôme
- Lin, Michael Z.
- Boyden, Edward S.
- Murphy, Gabe J.
- Waters, Jack
- Li, Lu
- Tasic, Bosiljka
- Zeng, Hongkui
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 174
- Issue
- 2
- Pages
- 465-480.e22
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6086366
- OpenAlex
- W2773803332
- Cited by
- 817
- References
- 43
- Citations by year
- 2026: 89 · 2025: 101 · 2024: 142 · 2023: 126 · 2022: 109 · 2021: 92 · 2020: 77 · 2019: 65 · 2018: 14
- FWCI
- 28.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- SSRN Electronic Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Allen Institute for Brain Science
- NIH (MH085500, DA028298, DA036909)
- Intelligence Advanced Research Projects Activity (D16PC00004)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- transgenic mouse lines, reporter lines, optogenetics, sparse labeling, brain cell types
- MeSH terms
- Animals, Brain, Calcium, Cell Line, Light, Mice, Transgenic, Microscopy, Fluorescence, Neurons, In Situ Hybridization, Fluorescence, Genes, Reporter, Transgenes, RNA, Untranslated, Mice, Gene Knockout Techniques, Optogenetics
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