# Genetic Strategies for Labeling AT2 Cells in Murine Lung via Abca3 and Etv5-Driven Reporters

**Authors:** Xue Liu, Xuexi Zhang, Zekun Li, Vrishika Kulur, Ningshan Liu, Jiurong Liang, Dianhua Jiang

PMC · DOI: 10.70322/jrbtm.2026.10002 · Journal of respiratory biology and translational medicine · 2026-03-28

## TL;DR

This study develops new genetic tools to label alveolar type 2 cells in mouse lungs for better understanding of lung biology and disease.

## Contribution

The novel contribution is the development of Abca3- and Etv5-driven inducible reporter systems for precise labeling of AT2 cells.

## Key findings

- Abca3 and Etv5 strategies effectively label AT2 cells across developmental stages.
- Both methods show high specificity and efficiency confirmed by flow cytometry and immunostaining.
- The systems can be used for tetO-mediated gene manipulation in AT2 cells.

## Abstract

Precise labeling of alveolar type 2 (AT2) cells is essential for elucidating lung development and injury responses. In this study, we evaluated Abca3 and Etv5-based genetic strategies for labeling AT2 cells in murine models. Using targeted genetic approaches, we generated Abca3-rtTA and Etv5-rtTA knock-in mouse lines and crossed them with pTRE-H2BGFP to create inducible reporter models driven by Abca3 or Etv5. Labeling specificity and efficiency were assessed by flow cytometry and co-immunostaining. Our results show that both Abca3 and Etv5 strategies faithfully label AT2 cells across developmental stages and following lung injury. Comprehensive analyses confirmed the high specificity and efficiency of labeling. These Abca3- and Etv5-driven systems offer robust tools for investigating AT2 cell biology and pathology and may serve as effective drivers for tetO-mediated gene knockout or overexpression studies specifically in AT2 cells in mouse models.

## Linked entities

- **Genes:** ABCA3 (ATP binding cassette subfamily A member 3) [NCBI Gene 21], ETV5 (ETS variant transcription factor 5) [NCBI Gene 2119]

## Full-text entities

- **Genes:** Sftpc (surfactant associated protein C) [NCBI Gene 20389] {aka Bricd6, SP-C, SP5, SPC, Sftp-2, Sftp2}, Slc39a8 (solute carrier family 39 (metal ion transporter), member 8) [NCBI Gene 67547] {aka 4933419D20Rik, BIGM103, ZIP-8, Zip8}, Pdpn (podoplanin) [NCBI Gene 14726] {aka E11, Gp38, OTS-8, RANDAM-2, T1-alpha, T1a}, Atxn1 (ataxin 1) [NCBI Gene 20238] {aka 2900016G23Rik, Atx1, Gm10786, Sca1}, Kras (Kras proto-oncogene, GTPase) [NCBI Gene 16653] {aka K-Ras, K-Ras 2, K-ras, Ki-ras, Kras-2, Kras2}, Abca3 (ATP-binding cassette, sub-family A member 3) [NCBI Gene 27410] {aka 1810036E22Rik, ABC-C, Abc3}, Fgfr2 (fibroblast growth factor receptor 2) [NCBI Gene 14183] {aka Bek, Fgfr-2, Fgfr-7, Fgfr2b, Fgfr7, KGFR}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Etv5 (ets variant 5) [NCBI Gene 104156] {aka 1110005E01Rik, 8430401F14Rik, ERM}, Epcam (epithelial cell adhesion molecule) [NCBI Gene 17075] {aka CD326, EGP, EGP-2, Egp314, Ep-CAM, EpCAM1}, Dnase1 (deoxyribonuclease I) [NCBI Gene 13419] {aka DNaseI, Dnl1}, ABCA3 (ATP binding cassette subfamily A member 3) [NCBI Gene 21] {aka ABC-C, ABC3, EST111653, LBM180, SMDP3}, Cd24a (CD24a antigen) [NCBI Gene 12484] {aka Cd24, HSA, Ly-52, nectadrin}, ETV5 (ETS variant transcription factor 5) [NCBI Gene 2119] {aka ERM}
- **Diseases:** tumorigenesis (MESH:D063646), lung cancer (MESH:D008175), fibrosis (MESH:D005355), lung adenocarcinoma (MESH:D000077192), AT2 (MESH:C567048), interstitial lung disease (MESH:D017563), IPF (MESH:D054990), neonatal respiratory failure (MESH:D012131), ARDS (MESH:D012128), pulmonary abnormalities (MESH:D008171), developmental defects (MESH:D000094602), inflammation (MESH:D007249), toxicity (MESH:D064420), lung injury (MESH:D055370)
- **Chemicals:** OCT (MESH:C051883), ethanol (MESH:D000431), PBS (MESH:D007854), Cyanine7 (-), doxycycline (MESH:D004318), biotin (MESH:D001710), H2O (MESH:D014867), lipid (MESH:D008055), AF647 (MESH:C569686), bleomycin (MESH:D001761), Cy5.5 (MESH:C098793), DAPI (MESH:C007293), sucrose (MESH:D013395), PFA (MESH:C003043), Tamoxifen (MESH:D013629), tetracycline (MESH:D013752)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** R288K
- **Cell lines:** AT2 — Homo sapiens (Human), Telomerase immortalized cell line (CVCL_VR37), C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025979/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC13025979/full.md

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Source: https://tomesphere.com/paper/PMC13025979