rtTA toxicity limits the usefulness of the SP-C-rtTA transgenic mouse
Open accessAbstract
The doxycycline (DOX)-inducible gene expression systems allow tight temporal and spatial control of transgene expression, invaluable in studies of organ development and disease pathogenesis. Transgenic mice using the human Surfactant Protein C promoter to drive the expression of the reverse tetracycline transactivator (SP-C-rtTA) enabled functional analysis of essential gene function during lung development. Here we report that DOX-fed SP-C-rtTA mice during the period in which Type II cells differentiate results in cellular toxicity that may have confounded the interpretation of previous reports using this line. These effects included impaired alveologenesis, loss/reduction in expression of surfactant-associated proteins, and death. Severity was dependent on genetic background: outbred mice or those on a CD1 background are highly susceptible, whereas the C57BL/6 background appeared resistant by morphological criteria. However, quantitative analysis reveled that DOX-fed, SP-C-rtTA C57BL/6 pups had reduced surfactant mRNA accumulation that could contribute to synthetic lethality when combined with other genetic alterations. We conclude that the combination of genetic backgrounds, length of DOX exposure and the presence of the SP-C-rtTA transgene contributed more than previously appreciated to the similarities seen in the phenotypes reported by investigators using the SP-C-rtTA, (tetO)(7)-Cre. These studies demonstrate the importance of using appropriate SP-C-rtTA only controls in all experiments.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In transgenic mice, toxic side-effects of tTA and rtTA have been reported.
“In transgenic mice, toxic side-effects of tTA and rtTA have also been reported [79-83].”
From Tet-On Systems For Doxycycline-inducible Gene Expression (2016) · cites this paper as [83]
The Results and Discussion report toxic effects of SP-C-rtTA in transgenic mice, particularly with doxycycline exposure during lung development. The passages do not report toxicity of tTA as a separate transactivator; despite one subsection heading saying “tTA/DOX,” its text discusses rtTA/DOX. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe severity of toxic side-effects of tTA and rtTA depends on the genetic background of the animal and possibly also on the (r)tTA version used.
“The severity of these effects depends on the genetic background of the animal and possibly also on the (r)tTA version used.”
From Tet-On Systems For Doxycycline-inducible Gene Expression (2016) · cites this paper as [83]
The Results and Discussion section on genetic background (page not supplied) shows that SP-C-rtTA toxicity differed between CD1 and C57BL/6 mice. The paper discusses one rtTA variant, but does not establish that toxicity severity depends on the (r)tTA version used or assess tTA toxicity generally. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Notch Signaling: Cell Fate Control and Signal Integration in Development
Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999) · Science · doi:10.1126/science.284.5415.770 · Cited by 5,909 · see citing works
Urlinger, S., Baron, U., Thellmann, M., Hasan, M. T., Bujard, H., & Hillen, W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130192197 · Cited by 928 · see citing works
Branda, C., & Dymecki, S. M. (2004) · Developmental Cell · doi:10.1016/s1534-5807(03)00399-x · Cited by 863 · see citing works
Inducible gene targeting in mice using the Cre/lox system.
Sauer, B. (1998) · Methods · doi:10.1006/meth.1998.0593 · Cited by 858 · see citing works
Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter.
Furth, P. A., St‐Onge, L., Boeger, H., Gruss, P., Gossen, M., Kistner, A., Bujard, H., & Hennighausen, L. G. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.20.9302 · Cited by 768 · see citing works
Adamson, I. Y. R., & Bowden, D. H. (1974) · PubMed · Cited by 713 · see citing works
Early restriction of peripheral and proximal cell lineages during formation of the lung
Perl, A. T., Wert, S. E., Nagy, A., Lobe, C. G., & Whitsett, J. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152238499 · Cited by 525 · see citing works
Notch–RBP-J signaling is involved in cell fate determination of marginal zone B cells
Tanigaki, K., Han, H., Yamamoto, N., Tashiro, K., Ikegawa, M., Kuroda, K., Suzuki, A., Nakano, T., & Honjo, T. (2002) · Nature Immunology · doi:10.1038/ni793 · Cited by 478 · see citing works
Vagaries of conditional gene targeting
Schmidt‐Supprian, M., & Rajewsky, K. (2007) · Nature Immunology · doi:10.1038/ni0707-665 · Cited by 417 · see citing works
β-Catenin Is Required for Specification of Proximal/Distal Cell Fate during Lung Morphogenesis
Mucenski, M. L., Wert, S. E., Nation, J. M., Loudy, D. E., Huelsken, J., Birchmeier, W., Morrisey, E. E., & Whitsett, J. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305892200 · Cited by 322 · see citing works
Compensatory Roles of Foxa1 and Foxa2 during Lung Morphogenesis*
Wan, H.-J., Dingle, S., Xu, Y., Besnard, V., Kaestner, K., Ang, S., Wert, S., Stahlman, M., & Whitsett, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414122200 · Cited by 297 · see citing works
Flodby, P., Barlow, C., Kylefjord, H., Åhrlund-Richter, L., & Xanthopoulos, K. G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.40.24753 · Cited by 293 · see citing works
Cre-mediated somatic site-specific recombination in mice.
Akagi, K., Sandig, V., Vooijs, M., van der Valk, M. V., Giovannini, M., Strauss, M., & Berns, A. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.9.1766 · Cited by 275 · see citing works
RIP-Cre Revisited, Evidence for Impairments of Pancreatic β-Cell Function
Lee, J., Ristow, M., Lin, X., White, M. F., Magnuson, M. A., & Hennighausen, L. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m512373200 · Cited by 246 · see citing works
Conditional gene expression in the respiratory epithelium of the mouse
Perl, A.-K. T., Tichelaar, J., & Whitsett, J. (2002) · Transgenic research · doi:10.1023/a:1013986627504 · Cited by 237 · see citing works
ABCA3 as a Lipid Transporter in Pulmonary Surfactant Biogenesis
Ban, N., Matsumura, Y., Sakai, H., Takanezawa, Y., Sasaki, M., Arai, H., & Inagaki, N. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611767200 · Cited by 222 · see citing works
Yanagi, S., Kishimoto, H., Kawahara, K., Sasaki, T., Sasaki, M., Nishio, M., Yajima, N., Hamada, K., Horie, Y., Kubo, H., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31854 · Cited by 170 · see citing works
Fitzgerald, M. L., Xavier, R. J., Haley, K. J., Welti, R., Goss, J. L., Brown, C. E., Zhuang, D. Z., Bell, S. A., Lu, N., McKee, M. L., et al. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600449-jlr200 · Cited by 170 · see citing works
ABCA3 Is Critical for Lamellar Body Biogenesis in Vivo
Cheong, N., Zhang, H., Madesh, M., Zhao, M., Yu, K. R. T., Dodia, C., Fisher, A. B., Savani, R. C., & Shuman, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703927200 · Cited by 154 · see citing works
Foxa2 is required for transition to air breathing at birth.
Wan, H.-J., Xu, Y., Ikegami, M., Stahlman, M., Kaestner, K., Ang, S., & Whitsett, J. (2004) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0404424101 · Cited by 152 · see citing works
SnapShot: Notch Signaling Pathway
Ilagan, M. X. G., & Kopan, R. (2007) · Cell · doi:10.1016/j.cell.2007.03.011 · Cited by 144 · see citing works
Self-citationC/EBPα is required for lung maturation at birth
Martis, P. C., Whitsett, J. A., Xu, Y. J., Perl, A. T., Wan, H., & Ikegami, M. (2006) · Development · doi:10.1242/dev.02273 · Cited by 141 · see citing works
Stat-3 is required for pulmonary homeostasis during hyperoxia
Hokuto, I., Ikegami, M., Yoshida, M., Takeda, K., Akira, S., Perl, A.-K. T., Hull, W. M., Wert, S. E., & Whitsett, J. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19491 · Cited by 128 · see citing works
Nguyen, N. M., Kelley, D. G., Schlueter, J. A., Meyer, M., Senior, R. M., & Miner, J. H. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.02.031 · Cited by 96 · see citing works
Expression of the Reverse Tetracycline-Transactivator Gene Causes Emphysema-Like Changes in Mice
Sisson, T. H., Hansen, J. M., Shah, M., Hanson, K. E., Du, M., Ling, T., Simon, R. H., & Christensen, P. J. (2006) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2005-0378oc · Cited by 75 · see citing works
Bassères, D. S. D. S., Levantini, E., Ji, H., Monti, S., Elf, S., Dayaram, T., Fenyus, M. L., Kocher, O. N., Golub, T. R., Wong, K., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.3.1109-1123.2006 · Cited by 69 · see citing works
Calcineurin/Nfat signaling is required for perinatal lung maturation and function
Dave, V. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27331 · Cited by 51 · see citing works
Genetic Disorders of Surfactant Homeostasis
Whitsett, J. A., Wert, S. E., & Xu, Y. J. (2005) · Neonatology · doi:10.1159/000084875 · Cited by 48 · see citing works
Sugahara, K., Iyama, K.-I., Kimura, T., Sano, K., Darlington, G., Akiba, T., & Takiguchi, M. (2001) · Cell and Tissue Research · doi:10.1007/s004410100420 · Cited by 45 · see citing works
Conditional Control of Gene Expression in the Respiratory Epithelium
Whitsett, J. A., & Perl, A. T. (2006) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.f310 · Cited by 42 · see citing works
(2007) · Nature · doi:10.1038/449378a · Cited by 15 · see citing works
Flagged first, then by citations
2 of the 33 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Tet-On Systems For Doxycycline-inducible Gene Expression
T. Das, A., Tenenbaum, L., & Berkhout, B. (2016) · Current Gene Therapy · doi:10.2174/1566523216666160524144041 · Cited by 434 · see citing works
“In transgenic mice, toxic side-effects of tTA and rtTA have also been reported [79-83].”
BackgroundPractical considerations for choosing a mouse model of Alzheimer’s disease
Jankowsky, J. L., & Zheng, H. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0231-7 · Cited by 449 · see citing works
Lentiviral vectors: basic to translational.
Sakuma, T., Barry, M., & Ikeda, Y. (2012) · Biochemical Journal · doi:10.1042/bj20120146 · Cited by 333 · see citing works
Morimoto, M., Liu, Z., Cheng, H., Winters, N., Bader, D. M., & Kopan, R. (2010) · Journal of Cell Science · doi:10.1242/jcs.058669 · Cited by 235 · see citing works
Self-citationMorimoto, M., Nishinakamura, R., Saga, Y., & Kopan, R. (2012) · Development · doi:10.1242/dev.083840 · Cited by 209 · see citing works
Self-citationSimple piggyBac transposon-based mammalian cell expression system for inducible protein production
Li, Z.-J., Michael, I., Zhou, D., Nagy, A., & Rini, J. (2013) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1218620110 · Cited by 161 · see citing works
A Nanobody-Based System Using Fluorescent Proteins as Scaffolds for Cell-Specific Gene Manipulation
Tang, J. C. Y., Szikra, T., Kozorovitskiy, Y., Teixiera, M., Sabatini, B. L., Roska, B., & Cepko, C. L. (2013) · Cell · doi:10.1016/j.cell.2013.07.021 · Cited by 112 · see citing works
Considerations and guidelines for mouse metabolic phenotyping in diabetes research
Alquier, T., & Poitout, V. (2017) · Diabetologia · doi:10.1007/s00125-017-4495-9 · Cited by 105 · see citing works
Han, H. J., Allen, C. C., Buchovecky, C. M., Yetman, M. J., Born, H. A., Marin, M. A., Rodgers, S. P., Song, B. J., Lu, H.-C., Justice, M. J., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0893-12.2012 · Cited by 105 · see citing works
Type I Alveolar Epithelial Cells Mount Innate Immune Responses during Pneumococcal Pneumonia
Yamamoto, K., Ferrari, J. D., Cao, Y. X., Ramirez, M. I., Jones, M. R., Quinton, L. J., & Mizgerd, J. P. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200634 · Cited by 94 · see citing works
Transferring a synthetic gene circuit from yeast to mammalian cells
Nevozhay, D., Żal, T., & Balázsi, G. (2013) · Nature Communications · doi:10.1038/ncomms2471 · Cited by 92 · see citing works
Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116
Yang, M., Hilton, M. B., Seaman, S., Haines, D. C., Nagashima, K., Burks, C., Tessarollo, L., Ivanova, P. T., Brown, H. A., Umstead, T. M., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.019 · Cited by 82 · see citing works
Bird, A. D., McDougall, A. R. A., Seow, B., Hooper, S. B., & Cole, T. J. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1362 · Cited by 81 · see citing works
The a“MAZE”ing World of Lung-Specific Transgenic Mice
Rawlins, E. L., & Perl, A. T. (2011) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0372ps · Cited by 73 · see citing works
Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways
Zhang, S., Loch, A. J., Radtke, F., Egan, S. E., & Xu, K. (2013) · Developmental Dynamics · doi:10.1002/dvdy.23965 · Cited by 53 · see citing works
Zhang, X. Z., Zhang, Y., Tao, B., Teng, L. S., Li, Y., Cao, R., Gui, Q., Ye, M., Mou, X., Cheng, H., et al. (2012) · The FASEB Journal · doi:10.1096/fj.11-200139 · Cited by 51 · see citing works
Habermehl, D., Parkitna, J. M. R., Kaden, S., Brügger, B., Wieland, F., Gröne, H., & Schütz, G. (2011) · Molecular Endocrinology · doi:10.1210/me.2009-0380 · Cited by 51 · see citing works
Gatward, L. F. D., Kennard, M. R., Smith, L. I. F., & King, A. (2021) · Diabetic Medicine · doi:10.1111/dme.14711 · Cited by 50 · see citing works
Bird, A. D., Choo, Y. L., Hooper, S. B., McDougall, A. R. A., & Cole, T. J. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0169oc · Cited by 46 · see citing works
Benabdellah, K., Cobo, M., Muñoz, P., Toscano, M. G., & Martı́n, F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023734 · Cited by 42 · see citing works
Simpson, D. S., Mason-Richie, N. A., Gettler, C. A., & Wikenheiser‐Brokamp, K. A. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1359 · Cited by 41 · see citing works
Li, A., Zhang, C., Gao, S., Chen, F., Yang, C., Luo, R., & Xiao, H. (2012) · Oncogene · doi:10.1038/onc.2012.253 · Cited by 38 · see citing works
Yetman, M. J., Lillehaug, S., Bjaalie, J. G., Leergaard, T. B., & Jankowsky, J. L. (2015) · Brain Structure and Function · doi:10.1007/s00429-015-1040-9 · Cited by 34 · see citing works
Estimating structural alterations in animal models of lung emphysema. Is there a gold standard?
Ochs, M. (2013) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2013.10.004 · Cited by 35 · see citing works
Glover, J. D., Taylor, L., Sherman, A., Zeiger-Poli, C., Sang, H., & McGrew, M. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077222 · Cited by 34 · see citing works
CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair
Hassan, D., & Chen, J. (2024) · Nature Communications · doi:10.1038/s41467-024-48632-3 · Cited by 34 · see citing works
Matsuzaki, Y., Oue, M., & Hirai, H. (2013) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2013.12.004 · Cited by 32 · see citing works
Ikeda, H., Shiojima, I., Oka, T., Yoshida, M., Maemura, K., Walsh, K., Igarashi, T., & Komuro, I. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00732-10 · Cited by 30 · see citing works
Pyo, K., Lim, S. M., Kim, H. R., Sung, Y. H., Yun, M. R., Kim, S., Kim, H., Kang, H. N., Lee, J. M., Kim, S. G., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.10.022 · Cited by 30 · see citing works
Developing tTA Transgenic Rats for Inducible and Reversible Gene Expression
Zhou, H., Huang, C., Yang, M., Landel, C. P., Xia, P. Y., Liu, Y., & Xia, X. (2009) · International Journal of Biological Sciences · doi:10.7150/ijbs.5.171 · Cited by 29 · see citing works
Li, X., Wang, L., Hao, J., Zhu, Q., Guo, M., Wu, C., Li, S., Guo, Q., Ren, Q., Bai, N., et al. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.64285 · Cited by 27 · see citing works
SPC-Cre-ERT2 Transgenic Mouse for Temporal Gene Deletion in Alveolar Epithelial Cells
Gui, Y.-S., Wang, L., Tian, X., Feng, R., Ma, A., Cai, B., Zhang, H., & Xu, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046076 · Cited by 22 · see citing works
Lent-On-Plus Lentiviral vectors for conditional expression in human stem cells
Benabdellah, K., Muñoz, P., Cobo, M., Gutiérrez-Guerrero, A., Sánchez-Hernández, S., García-Pérez, A., Anderson, P. O., Carrillo-Gálvez, A. B., Toscano, M. G., & Martı́n, F. (2016) · Scientific Reports · doi:10.1038/srep37289 · Cited by 19 · see citing works
Jia, W., Jiang, S., Tang, Q., Shen, D., Xue, B., Ning, W., & Li, C. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.01.021 · Cited by 15 · see citing works
The widely used Ucp1-Cre transgene elicits complex developmental and metabolic phenotypes
Halurkar, M. S., Inoue, O., Singh, A., Mukherjee, R., Ginugu, M., Ahn, C., Paese, C. L. B., Duszynski, M., Brugmann, S. A., Lim, H., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-54763-4 · Cited by 14 · see citing works
Yang, Y.-S., Yang, M.-C. W., Guo, Y., Williams, O. W., & Weissler, J. C. (2009) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00144.2009 · Cited by 11 · see citing works
A molecular circuit regulates fate plasticity in emerging and adult AT2 cells
Sawhney, A. S., Deskin, B., Cai, J., Gibbard, D. F., Ali, G., Utoft, A., Qi, X., Olson, A., Hausman, H., Sabol, L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64224-1 · Cited by 10 · see citing works
Tristán‐Manzano, M., Maldonado‐Pérez, N., Justicia-Lirio, P., Cortijo-Gutierréz, M., Tristán-Ramos, P., Blanco-Benítez, C., Pavlovic, K., Aguilar-González, A., Muñoz, P., Molina-Estévez, F. J., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.03.018 · Cited by 10 · see citing works
Stein, L. R., Zorumski, C. F., Imai, S., & Izumi, Y. (2015) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.10.005 · Cited by 10 · see citing works
Smith, R. W., Hicks, D. A., & Reynolds, S. D. (2011) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0099oc · Cited by 10 · see citing works
Efficiency and Specificity of Gene Deletion in Lung Epithelial Doxycycline-Inducible Cre Mice
Sinha, M., & Lowell, C. A. (2017) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0208oc · Cited by 10 · see citing works
An, K., Liu, H., Xiao-long, Z., Deng, D. Y. B., Zhang, J.-J., & Liu, Z. (2017) · Stem Cells International · doi:10.1155/2017/6082684 · Cited by 10 · see citing works
Antony, N., McDougall, A. R. A., Mantamadiotis, T., Cole, T. J., & Bird, A. D. (2016) · Scientific Reports · doi:10.1038/srep25569 · Cited by 10 · see citing works
Tetracycline Regulator Expression Alters the Transcriptional Program of Mammalian Cells
Hackl, H., Rommer, A., Konrad, T. A., Nassimbeni, C., & Wieser, R. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013013 · Cited by 8 · see citing works
Justicia-Lirio, P., Tristán‐Manzano, M., Maldonado‐Pérez, N., Barbero-Jiménez, C., Cortijo-Gutierréz, M., Pavlovic, K., Molina-Estévez, F. J., Muñoz, P., Hinckley-Boned, A., Rodríguez-Madoz, J. R., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102308 · Cited by 7 · see citing works
Qiu, Z., Zhou, J.-S., Liu, F., Qin, X., Dai, Y., Ke, Y., Chen, Z., Li, W., Ying, S., & Shen, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177334 · Cited by 7 · see citing works
Michael, H. T., Graff‐Cherry, C., Chin, S., Rauck, C., Habtemichael, A. D., Bunda, P., Smith, T. M., Campos, M. M., Bharti, K., Arnheiter, H., et al. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-25186 · Cited by 5 · see citing works
Generating Beta-Cell-Specific Transgenic Mice Using the Cre-Lox System
Smith, L. I. F., Hill, T. G., & Bowe, J. E. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0385-7_13 · Cited by 5 · see citing works
Correspondence: T cells are compromised in tetracycline transactivator transgenic mice
Schmitt, A., Schulze‐Osthoff, K., & Hailfinger, S. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-017-0042-y · Cited by 5 · see citing works
The Regulation of Branching Morphogenesis in the Developing Lung
Chen, J. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-319-21082-7_1 · Cited by 4 · see citing works
Development of a Chromosomally Integrated Metabolite-Inducible Leu3p-α-IPM “Off-On” Gene Switch
Poulou, M., Bell, D. M., Bozonelos, K., Alexiou, M. V., Gavalas, A., Lovell-Badge, R. H., & Remboutsika, E. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012488 · Cited by 4 · see citing works
Linesch, P. W., Akhtar, A. A., & Breunig, J. J. (2023) · Current Protocols · doi:10.1002/cpz1.792 · Cited by 3 · see citing works
Modulation of Myeloid Cell Function Using Conditional and Inducible Transgenic Approaches
McCubbrey, A. L., & Janssen, W. J. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8570-8_13 · Cited by 2 · see citing works
Hot iron branding--not a reasonable requirement for international trade in live ruminants.
Whiting, T. L. (2005) · PubMed Central · Cited by 2 · see citing works
Metabolic syndrome in mice induced by expressing a transcriptional activator in adipose tissue
Zhang, L., Zhou, Y., Zhu, A. Y., Li, X.-Q., Mundt, S. S., Gao, L., Lisnock, J., Hernandez, M., Alonso‐Galicia, M., Springer, M. S., et al. (2011) · Transgenic Research · doi:10.1007/s11248-011-9562-2 · Cited by 1 · see citing works
Protein Transfection of Mouse Lung
Geraghty, P. M., & Foronjy, R. (2013) · Journal of Visualized Experiments · doi:10.3791/50080 · Cited by 1 · see citing works
Akhtar, A. A., & Breunig, J. J. (2017) · Current Protocols in Stem Cell Biology · doi:10.1002/cpsc.28 · Cited by 1 · see citing works
The widely used Ucp1-Cre Evdr transgene elicits complex developmental and metabolic phenotypesPreprint
Halurkar, M. S., Inoue, O., Mukherjee, R., Paese, C. L. B., Duszynski, M., Brugmann, S. A., Lim, H., & Sánchez-Gurmaches, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.20.563165 · Cited by 1 · see citing works
DETERMINING THE GENOTYPE-PHENOTYPE CONNECTION IN SYNTHETIC INDUCIBLE GENE EXPRESSION SYSTEMS
Adams, R. (2012) · Digital Commons-TMC (Texas Medical Center)
Iannucci, V. (2013) · Ghent University Academic Bibliography (Ghent University)
Justicia-Lirio, P., Tristán‐Manzano, M., Maldonado‐Pérez, N., Barbero-Jiménez, C., Cortijo-Gutierréz, M., Pavlovic, K., Molina-Estévez, F. J., Muñoz, P., Hinckley-Boned, A., Griñán‐Lisón, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.23.576842
- Authors
- Morimoto, M., & Kopan, R.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Kopan, Raphael
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 325
- Issue
- 1
- Pages
- 171-178
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC2955437
- OpenAlex
- W2037335708
- Cited by
- 62
- References
- 33
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 11 · 2012: 8
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1658 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Toyobo Biotechnology Foundation
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK066408)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 044056, R01HD044056)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- reverse tetracycline transactivator, surfactant protein C promoter, inducible gene expression, alveolarization, genetic background effects, synthetic lethality, lung development
- MeSH terms
- Animals, Cell Survival, Doxycycline, Mice, Transgenic, Phenotype, Pulmonary Alveoli, Tetracycline, Trans-Activators, Survival Analysis, Pulmonary Surfactant-Associated Protein C, Embryonic Development, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
