New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo
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Astrocytes exist throughout the nervous system and are proposed to affect neural circuits and behavior. However, studying astrocytes has proven difficult because of the lack of tools permitting astrocyte-selective genetic manipulations. Here, we report the generation of Aldh1l1-Cre/ERT2 transgenic mice to selectively target astrocytes in vivo. We characterized Aldh1l1-Cre/ERT2 mice using imaging, immunohistochemistry, AAV-FLEX-GFP microinjections, and crosses to RiboTag, Ai95, and new Cre-dependent membrane-tethered Lck-GCaMP6f knockin mice that we also generated. Two to three weeks after tamoxifen induction, Aldh1l1-Cre/ERT2 selectively targeted essentially all adult (P80) brain astrocytes with no detectable neuronal contamination, resulting in expression of cytosolic and Lck-GCaMP6f, and permitting subcellular astrocyte calcium imaging during startle responses in vivo. Crosses with RiboTag mice allowed sequencing of actively translated mRNAs and determination of the adult cortical astrocyte transcriptome. Thus, we provide well-characterized, easy-to-use resources with which to selectively study astrocytes in situ and in vivo in multiple experimental scenarios.
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Astrocytes synthesize most of CNS ApoE.
“Because astrocytes synthesize most of CNS ApoE and were the cell type most affected by the global E4 to E2 transition, we generated APOE4s2loxP/loxP/Aldh1l1-CreERT2 APOE switch mice (APOE4s2A) that would express APOE4 in all CNS cell types except for astrocytes, which would selectively transition to APOE2 upon TAM injection29,30 (Fig. 4a).”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [30]
The Results and Discussion describe an adult cortical astrocyte transcriptome, but do not state how much CNS ApoE astrocytes synthesize. Searches for ApoE and apolipoprotein E found no passage in our copy addressing that proportion. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThe AldH1L1 promoter seems to have widespread CNS efficiency.
“Promising in this respect is the recent availability of the AldH1L1 promoter, which seems to have widespread CNS efficiency 144, 145 .”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [144]
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- Authors
- Srinivasan, R., Lu, T.-Y., Chai, H., Xu, J., Huang, B. S., Golshani, P., Coppola, G., & Khakh, B. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Khakh, Baljit S.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 92
- Issue
- 6
- Pages
- 1181-1195
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5403514
- OpenAlex
- W2559768163
- Cited by
- 443
- References
- 43
- Citations by year
- 2026: 29 · 2025: 66 · 2024: 52 · 2023: 73 · 2022: 51 · 2021: 58 · 2020: 46 · 2019: 27 · 2018: 26 · 2017: 14 · 2016: 1
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (MH099559, MH104069, MH106197)
- NINDS Informatics Center for Neurogenetics and Neurogenomics at UCLA (P30 NS062691)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- astrocytes, tamoxifen-inducible Cre, astrocyte processes, RiboTag, startle response, transgenic mouse lines
- MeSH terms
- Aldehyde Dehydrogenase, Animals, Astrocytes, Calcium, Cytosol, Mice, Transgenic, RNA, Messenger, Tamoxifen, Integrases, Calcium Signaling, Selective Estrogen Receptor Modulators, Gene Expression Profiling, Models, Animal, Estrogen Receptor beta, GABA Plasma Membrane Transport Proteins, Mice
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