The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Metabolic Pitfalls of CNS Cre-Based Technology
Open accessAbstract
Nestin-Cre mice have a significant metabolic phenotype that is hard to discern from current literature. Indeed, the Cre-lox system has numerous problems that can affect physiological parameters, and these are missed when the correct control strains are not used. Despite the increasing use of the Cre-lox system, these issues were not visible to the scientific community previously and may have affected published work. This makes it important to highlight the issues and raise awareness of the pitfalls of the Cre-lox system. Therefore, this perspective will discuss the impact of CNS and peripheral "off-target" Cre recombination on metabolic systems and describe the development of new approaches to obviate the difficulties.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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 the citing paper
“However, these studies were confounded by the fact that ap2-Cre transgenic mice also express Cre recombinase in nonadipose tissues, including in the CNS (47).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [47]
Citations
Cites
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., & Schütz, G. (1999) · Nature Genetics · doi:10.1038/12703 · Cited by 1,841
Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Krashes, M. J., Koda, S., Ye, C., Rogan, S. C., Adams, A. C., Cusher, D. S., Maratos-Flier, E., Roth, B. L., & Lowell, B. B. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46229 · Cited by 1,578
Genetic transformation of mouse embryos by microinjection of purified DNA.
Gordon, J. W., Scangos, G. A., Plotkin, D. J., Barbosa, J. A., & Ruddle, F. H. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.12.7380 · Cited by 1,425
Crawley, J. N., Belknap, J. K., Collins, A. C., Crabbe, J. C., Frankel, W. N., Henderson, N. D., HITZEMANN, R. J., Maxson, S. C., Miner, L. L., Silva, A. J., et al. (1997) · Psychopharmacology · doi:10.1007/s002130050327 · Cited by 1,372
Alexander, G. M., Rogan, S. C., Abbas, A. I., Armbruster, B. N., Pei, Y., Allen, J., Nonneman, R. J., Hartmann, J. F., Moy, S. S., Nicolelis, M. A. L., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.014 · Cited by 1,019
Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose Tissue
Halberg, N., Khan, T., Trujillo, M. E., Wernstedt-Asterholm, I., Attie, A. D., Sherwani, S., Wang, Z. V., Landskroner-Eiger, S., Dineen, S., Magalang, U. J., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00192-09 · Cited by 896
Branda, C., & Dymecki, S. M. (2004) · Developmental Cell · doi:10.1016/s1534-5807(03)00399-x · Cited by 876
Bacteriophage P1 site-specific recombination
Sternberg, N. L., & Hamilton, D. L. (1981) · Journal of Molecular Biology · doi:10.1016/0022-2836(81)90375-2 · Cited by 813
Immune responses to gene therapy vectors: influence on vector function and effector mechanisms
Bessis, N., Garcia-Cozar, F. J., & Boissier, M. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302364 · Cited by 653
Neuronal PTP1B regulates body weight, adiposity and leptin action
Bence, K. K., Delibegovic, M., Xue, B., Gorgun, C. Z., Hotamisligil, G. S., Neel, B. G., & Kahn, B. B. (2006) · Nature Medicine · doi:10.1038/nm1435 · Cited by 633
Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells
Loonstra, A., Vooijs, M., Beverloo, H. B., Allak, B. A., van Drunen, E., Kanaar, R., Berns, A. J. M., & Jonkers, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161269798 · Cited by 591
Fate mapping Nkx2.1‐lineage cells in the mouse telencephalon
Xu, Q., Tam, M., & Anderson, S. A. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21529 · Cited by 560
Introduction of a rabbit β-globin gene into the mouse germ line
Costantini, F., & Lacy, E. (1981) · Nature · doi:10.1038/294092a0 · Cited by 460
Thompson, S., Clarke, A. R., Pow, A. M., Hooper, M., & Melton, D. W. (1989) · Cell · doi:10.1016/0092-8674(89)90905-7 · Cited by 425
Gao, Q., Wolfgang, M. J., Neschen, S., Morino, K., Horvath, T. L., Shulman, G. I., & Fu, X.-Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0303992101 · Cited by 385
Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids
Schmidt, E. E., Taylor, D., Prigge, J. R., Barnett, S., & Capecchi, M. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240471297 · Cited by 335
Epithelial-Specific Cre/lox Recombination in the Developing Kidney and Genitourinary Tract
Shao, X., Somlo, S., & Igarashi, P. (2002) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000016444.90348.50 · Cited by 332
Lessons on Conditional Gene Targeting in Mouse Adipose Tissue
Lee, K. Y., Russell, S. J., Ussar, S., Boucher, J., Vernochet, C., Mori, M. A., Smyth, G., Rourk, M., Cederquist, C., Rosen, E. D., et al. (2013) · Diabetes · doi:10.2337/db12-1089 · Cited by 328
Padilla, S. L., Carmody, J. S., & Zeltser, L. M. (2010) · Nature Medicine · doi:10.1038/nm.2126 · Cited by 312
Mammalian genomes contain active recombinase recognition sites
Thyagarajan, B., Guimarães, M. J., Groth, A. C., & Calos, M. P. (2000) · Gene · doi:10.1016/s0378-1119(00)00008-1 · Cited by 289
Schonhoff, S. E., Giel–Moloney, M., & Leiter, A. B. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.03.013 · Cited by 285
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 252
Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1–deficient mice
Yakar, S., Setser, J., Zhao, H., STANNARD, B. S., Haluzı́k, M., Glatt, V., Bouxsein, M., Kopchick, J. J., & LeRoith, D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci17763 · Cited by 249
Pfeifer, A., Brandon, E. P., Kootstra, N. A., Gage, F. H., & Verma, I. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201415498 · Cited by 224
Xu, Q., Guo, L., Moore, H., Waclaw, R. R., Campbell, K., & Anderson, S. A. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.004 · Cited by 218
Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1–deficient mice
Yakar, S., Setser, J., Zhao, H., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200417763 · Cited by 201
Adeno-associated virus effectively mediates conditional gene modification in the brain
Kaspar, B. K., Vissel, B., Bengoechea, T. G., Crone, S. A., Randolph‐Moore, L., Müller, R., Brandon, E. P., Schaffer, D. V., Verma, I. M., Lee, K., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042678699 · Cited by 196
Pancreas-Specific Cre Driver Lines and Considerations for Their Prudent Use
Magnuson, M. A., & Osipovich, A. B. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.06.011 · Cited by 182
Dubois, N. C., Hofmann, D., Kaloulis, K., Bishop, J. M., & Trumpp, A. (2006) · genesis · doi:10.1002/dvg.20226 · Cited by 181
Conditional gene targeting on the pure C57BL/6 genetic background
Mishina, M., & Sakimura, K. (2007) · Neuroscience Research · doi:10.1016/j.neures.2007.01.004 · Cited by 175
Conditional transgenic technologies.
Ryding, A., Sharp, M., & Mullins, J. J. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1710001 · Cited by 171
Forni, P. E., Scuoppo, C., Imayoshi, I., Taulli, R., Dastrù, W., Sala, V., Betz, U. A. K., Muzzi, P., Martinuzzi, D., Vercelli, A., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2815-06.2006 · Cited by 167
Neural crest expression of Cre recombinase directed by the proximal Pax3 promoter in transgenic mice
Li, J., Chen, F., & Epstein, J. A. (2000) · genesis · doi:10.1002/(sici)1526-968x(200002)26:2 · Cited by 158
Cre activity causes widespread apoptosis and lethal anemia during embryonic development
Naiche, L. A., & Papaioannou, V. E. (2007) · genesis · doi:10.1002/dvg.20353 · Cited by 148
The advent of AAV9 expands applications for brain and spinal cord gene delivery
Dayton, R. D., Wang, D. B., & Klein, R. L. (2012) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2012.681463 · Cited by 144
Nestin expression in pancreatic exocrine cell lineages
Delacour, A., Népote, V., Trumpp, A., & Herrera, P. L. (2003) · Mechanisms of Development · doi:10.1016/j.mod.2003.11.004 · Cited by 142
Tamoxifen-Induced Cre-loxP Recombination Is Prolonged in Pancreatic Islets of Adult Mice
Reinert, R. B., Kantz, J., Misfeldt, A. A., Poffenberger, G., GANNON, M. A., Briššová, M., & Powers, A. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033529 · Cited by 140
Padilla, S. L., Reef, D. K., & Zeltser, L. M. (2011) · Endocrinology · doi:10.1210/en.2011-1665 · Cited by 120
Deficiency of corpus callosum varies with strain and supplier of the mice
Wahłsten, D. (1982) · Brain Research · doi:10.1016/0006-8993(82)90513-3 · Cited by 114
Takano, A., Haruta, T., Iwata, M., Usui, I., Uno, T., Kawahara, J., Ueno, E., Sasaoka, T., & Kobayashi, M. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1891 · Cited by 109
Liang, H., Hippenmeyer, S., & Ghashghaei, H. T. (2012) · Biology Open · doi:10.1242/bio.20122287 · Cited by 107
Brain expression of Cre recombinase driven by pancreas‐specific promoters
Song, J., Xu, Y., Hu, X., Choi, B. J., & Tong, Q. (2010) · genesis · doi:10.1002/dvg.20672 · Cited by 107
Ahmed, B. Y., Chakravarthy, S., Eggers, R., Hermens, W. T., Zhang, J. Y., Niclou, S. P., Levelt, C. N., Sablitzky, F., Anderson, P. N., Lieberman, A. R., et al. (2004) · BMC Neuroscience · doi:10.1186/1471-2202-5-4 · Cited by 105
Martens, K., Bottelbergs, A., & Baes, M. I. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.061 · Cited by 100
Genetically manipulated mice: a powerful tool with unsuspected caveats
Matthaei, K. I. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.134908 · Cited by 96
Hoesche, C., Sauerwald, A., Veh, R. W., Krippl, B., & Kilimann, M. W. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74341-5 · Cited by 93
Synapsin I Cre transgene expression in male mice produces germline recombination in progeny
Rempe, D. A., Vangeison, G., Hamilton, J., Li, Y., Jepson, M., & Federoff, H. J. (2006) · genesis · doi:10.1002/gene.20183 · Cited by 88
Rein, M. L., & Deussing, J. M. (2011) · Molecular Genetics and Genomics · doi:10.1007/s00438-011-0663-7 · Cited by 84
A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods
Mullican, S. E., Tomaru, T., Gaddis, C. A., Peed, L. C., Sundaram, A., & Lazar, M. A. (2013) · Molecular Endocrinology · doi:10.1210/me.2012-1267 · Cited by 83
Galichet, C., Lovell-Badge, R. H., & Rizzoti, K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011443 · Cited by 76
Briançon, N., McNay, D. E. G., Maratos–Flier, E., & Flier, J. S. (2010) · Diabetes · doi:10.2337/db10-0481 · Cited by 61
A chemical-genetic approach for precise spatio-temporal control of cellular signaling
Dong, S., Allen, J., Farrell, M. S., & Roth, B. L. (2010) · Molecular BioSystems · doi:10.1039/c002568m · Cited by 55
Mazur, P. K., Grüner, B. M., Nakhai, H., Sipos, B., Zimber‐Strobl, U., Strobl, L. J., Radtke, F., Schmid, R. M., & Siveke, J. T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013578 · Cited by 39
Kocalis, H. E., Turney, M. K., Printz, R. L., Laryea, G. N., Muglia, L. J., Davies, S. S., Stanwood, G. D., McGuinness, O. P., & Niswender, K. D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042981 · Cited by 35
Price, V. J., Wang, L., & D’Mello, S. R. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23170 · Cited by 28
Qiu, L., Rivera‐Pérez, J. A., & Xu, Z. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018778 · Cited by 24
Honig, G., Liou, A., Berger, M., German, M. S., & Tecott, L. H. (2010) · Journal of Biomedical Science · doi:10.1186/1423-0127-17-82 · Cited by 23
Zhang, J., Wang, Y., Gao, Z., Yun, Z., & Ye, J. (2011) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2011.05656.x · Cited by 20
Molecular biology and biotechnology
(2009) · Choice Reviews Online · doi:10.5860/choice.47-0856 · Cited by 12
Rat Synapsin 1 Promoter Mediated Transgene Expression in Testicular Cell Types
Street, K. A., Xu, G., HALL, K. L., Intano, G. W., McCarrey, J. R., Herbert, D. C., Kilimann, M. W., & Walter, C. A. (2005) · DNA and Cell Biology · doi:10.1089/dna.2005.24.133 · Cited by 10
A pink mouse reports the switch from red to green fluorescence upon Cre-mediated recombination
Hartwich, H., Satheesh, S. V., & Nothwang, H. G. (2012) · BMC Research Notes · doi:10.1186/1756-0500-5-296 · Cited by 7
Addendum: Neuronal PTP1B regulates body weight, adiposity and leptin action
Bence, K. K., Delibegović, M., Xue, B., Görgün, C. Z., Hotamışlıgil, G. S., Neel, B. G., & Kahn, B. B. (2010) · Nature Medicine · doi:10.1038/nm0210-237b · Cited by 2
Cited by
Sorted by citations
Nestin-expressing progenitor cells: function, identity and therapeutic implications
Bernal, A., & Arranz, L. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2794-z · Cited by 415
A novel m6A reader Prrc2a controls oligodendroglial specification and myelination
Wu, R., Li, A., Sun, B., Sun, J.-G., Zhang, J., Zhang, T., Chen, Y., Xiao, Y., Gao, Y., Zhang, Q., et al. (2019) · Cell Research · doi:10.1038/s41422-018-0113-8 · Cited by 366
FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms
BonDurant, L. D., Ameka, M., Naber, M. C., Markan, K. R., Idiga, S. O., Acevedo, M. R., Walsh, S. A., Ornitz, D. M., & Potthoff, M. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.005 · Cited by 330
Zhang, Q., Delessa, C. T., Augustin, R., Bakhti, M., Colldén, G., Drucker, D. J., Feuchtinger, A., Caceres, C. G., Grandl, G., Harger, A., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.01.015 · Cited by 322
Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons
Furigo, I. C., Teixeira, P. D. S., de Souza, G. O., Couto, G. C. L., Romero, G. G., Perelló, M., Frazão, R., Elias, L. L. K., Metzger, M., List, E. O., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08607-1 · Cited by 230
Metadata
- Authors
- Harno, E., Cottrell, E. C., & White, A.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- White, Anne
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 18
- Issue
- 1
- Pages
- 21-28
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2093032500
- Cited by
- 200
- References
- 64
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 5 · 2023: 14 · 2022: 17 · 2021: 13 · 2020: 21 · 2019: 25 · 2018: 18 · 2017: 20 · 2016: 16 · 2015: 18 · 2014: 12 · 2013: 5
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- AstraZeneca
- National Institute for Health and Care Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- Cre-loxP system, central nervous system, metabolic phenotypes, control strains, conditional gene targeting
- MeSH terms
- Animals, Central Nervous System, DNA Nucleotidyltransferases, Protein-Lysine 6-Oxidase, Mice, Transgenic, Recombination, Genetic, Extracellular Matrix Proteins, Mice, Knockout, Gene Targeting, Integrases, Models, Animal, Mice, Nestin
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