ArticleNeuron2020
Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.
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Article in Neuron, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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124 citing papers in PubMed, 193 citations in OpenAlex.
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64 more citing papers are in PubMed but not listed here.
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Authors and funding
56 authors at 20 institutions in 6 countries.
Lin LuoDjavad Mowafaghian Centre for Brain Health and Department of Psychiatry, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
Mateusz C AmbrozkiewiczDepartment of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany; Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.
Fritz BenselerDepartment of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.
Cui ChenState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Emilie DumontierDepartment of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Susanne FalknerBiozentrum of the University of Basel, Basel, Switzerland.
Elisabetta FurlanisBiozentrum of the University of Basel, Basel, Switzerland.
Andrea M GomezBiozentrum of the University of Basel, Basel, Switzerland.
Naosuke HoshinaF.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Wei-Hsiang HuangDepartment of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal, QC H3G 1A4, Canada.
Mary Anne HutchisonSynapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Yu Itoh-MaruokaDivision of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Laura A LaveryDepartment of Molecular and Human Genetics, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77003, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Wei LiState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Tomohiko MaruoDivision of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Department of Biochemistry, Tokushima University Graduate School of Medical Sciences, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan; Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
Junko MotohashiDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Emily Ling-Lin PaiNina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Kenneth A PelkeySection on Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Ariane PereiraDepartment of Neurobiology and Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Thomas PhilipsDepartment of Neurology and Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jennifer L SinclairDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Jeff A StogsdillDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02139, USA.
Lisa TraunmüllerBiozentrum of the University of Basel, Basel, Switzerland.
Jiexin WangDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Joke WortelDepartment of Functional Genomics and Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and University Medical Center Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
Wenjia YouDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Departments of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Nashat AbumariaState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China; Department of Laboratory Animal Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Kevin T BeierDepartment of Physiology and Biophysics, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA 92697, USA.
Nils BroseDepartment of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.
Harold A BurgessDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Constance L CepkoDepartments of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Jean-François CloutierDepartment of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Cagla ErogluDepartment of Cell Biology, Department of Neurobiology, and Duke Institute for Brain Sciences, Regeneration Next Initiative, Duke University Medical Center, Durham, NC 27710, USA.
Sandra GoebbelsDepartment of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.
Pascal S KaeserDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Jeremy N KayDepartment of Neurobiology and Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Wei LuSynapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Liqun LuoDepartment of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Kenji MandaiDivision of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
Chris J McBainSection on Cellular and Synaptic Physiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Klaus-Armin NaveDepartment of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.
Marco A M PradoRobarts Research Institute, Department of Anatomy and Cell Biology, and Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5B7, Canada; Brain and Mind Institute, The University of Western Ontario, London, ON N6A 5B7, Canada.
Vania F PradoRobarts Research Institute, Department of Anatomy and Cell Biology, and Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5B7, Canada; Brain and Mind Institute, The University of Western Ontario, London, ON N6A 5B7, Canada.
Jeffrey RothsteinDepartment of Neurology and Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
John L R RubensteinNina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Gesine SaherDepartment of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.
Kenji SakimuraDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Joshua R SanesCenter for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Peter ScheiffeleBiozentrum of the University of Basel, Basel, Switzerland.
Yoshimi TakaiDivision of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Hisashi UmemoriF.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Matthijs VerhageDepartment of Functional Genomics and Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and University Medical Center Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam, the Netherlands.
Michisuke YuzakiDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Huda Yahya ZoghbiDepartment of Molecular and Human Genetics, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77003, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Hiroshi KawabeDepartment of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany; Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Department of Gerontology, Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, 2-2 Minatojima-minamimachi Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: kawabe@em.mpg.de.
Ann Marie CraigDjavad Mowafaghian Centre for Brain Health and Department of Psychiatry, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. Electronic address: acraig@mail.ubc.ca.
Harvard University · USMax Planck Institute of Experimental Medicine · DEUniversity of Basel · CHKobe University · JPNational Institutes of Health · USUniversity of British Columbia · CADuke University · USDuke University Hospital · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USJohns Hopkins Medicine · USKeio University Hospital · JPMontreal Neurological Institute and Hospital · CAState Key Laboratory of Medical NeurobiologyUniversity of California, San Francisco · USWestern University · CABaylor College of Medicine · USFudan University · CNHoward Hughes Medical Institute · USHumboldt-Universität zu Berlin · DEMcGill University Health Centre · CA
Funding
Cellular And Synaptic Physiology Of Hippocampal InterneuronsZIAHD001205 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MCBAIN, CHRIS J. · 2009 to 2025
$45.8MThe regulation of synaptic transmission and neural circuit functionZIANS003136 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI LU, WEI · 2012 to 2025
$27.0MNeuronal Circuits Controlling Behavior: Genetic Analysis in ZebrafishZIAHD008884 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BURGESS, HAROLD · 2009 to 2025
$21.3MViral ModuleP30EY012196 · NEI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MARGARET S LIVINGSTONE · 1998 to 2026
$21.3MVISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Goldis Malek · 1985 to 2026
$19.3MPreclinical and Clincial OutcomesP50HD103555 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI Sandesh Chakravarthy Sreenath Nagamani, David Loren Nelson · 2020 to 2026
$9.9MGenetic Control of Basal Telencephalic DevelopmentR01MH081880 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUBENSTEIN, JOHN L. R. · 2009 to 2023
$8.1MMOLECULAR PATHOGENESIS STUDIES OF RETT SYNDROMER01NS057819 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI ZOGHBI, HUDA Y · 2006 to 2025
$7.5MMosaic Analysis with Double Markers in MiceR01NS050835 · NINDS · STANFORD UNIVERSITY · PI LIQUN LUO · 2005 to 2026
$7.3MHow do neurons in the brain decide to refine their synaptic connections in vivo?R01MH111647 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI Chinfei Chen, Hisashi Umemori · 2017 to 2026
$6.8MGenetic Studies of Cortex Structure and DevelopmentR01NS099099 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUBENSTEIN, JOHN L. R. · 2016 to 2025
$6.4MDissecting the assembly of vertebrate neurotransmitter release sites-Research Supplements to Promote Diversity in Health-Related ResearchR01MH113349 · NIMH · HARVARD MEDICAL SCHOOL · PI Pascal Simon Kaeser · 2017 to 2026
$6.1MHoward Hughes Medical InstituteNEI NIH HHS P30 EY005722NEI NIH HHS P30 EY012196NEI NIH HHS R01 EY024694NEI NIH HHS R01 EY030611NICHD NIH HHS K99 HD092545NICHD NIH HHS P50 HD103555NIDA NIH HHS F32 DA038913NIDA NIH HHS K99 DA041445NIDA NIH HHS R00 DA041445NIDA NIH HHS R01 DA031833NIDA NIH HHS R01 DA042744NIMH NIH HHS R01 MH049428NIMH NIH HHS R01 MH081880NIMH NIH HHS R01 MH111647NIMH NIH HHS R01 MH113349NIMH NIH HHS R37 MH049428NINDS NIH HHS F31 NS092419NINDS NIH HHS R01 NS050835NINDS NIH HHS R01 NS057819NINDS NIH HHS R01 NS083898NINDS NIH HHS R01 NS092578NINDS NIH HHS R01 NS099099NINDS NIH HHS R01 NS102237NINDS NIH HHS R01 NS103484NINDS NIH HHS R37 NS029169
Abstract
The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities.
Indexed as
AnimalsFemaleGenes, ReporterGene TargetingGerm CellsIntegrasesMaleMiceMice, TransgenicMosaicismNeuronsOocytesRecombination, GeneticSpermatozoaCre recombinaseIntegrasesconditional gene targetingconditional knockinconditional knockoutconditional reporterCre-loxgermline recombinationmolecular geneticsmosaic recombinationparental sex biassite-specific recombinase
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