Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors

Luo, Lin and Ambrozkiewicz, Mateusz C. and Benseler, Fritz and Chen, Cui and Dumontier, Emilie and Falkner, Susanne and Furlanis, Elisabetta and Gomez, Andrea M. and Hoshina, Naosuke and Huang, Wei-Hsiang and Hutchison, Mary Anne and Itoh-Maruoka, Yu and Lavery, Laura A. and Li, Wei and Maruo, Tomohiko and Motohashi, Junko and Pai, Emily Ling-Lin and Pelkey, Kenneth A. and Pereira, Ariane and Philips, Thomas and Sinclair, Jennifer L. and Stogsdill, Jeff A. and Traunmüller, Lisa and Wang, Jiexin and Wortel, Joke and You, Wenjia and Abumaria, Nashat and Beier, Kevin T. and Brose, Nils and Burgess, Harold A. and Cepko, Constance L. and Cloutier, Jean-François and Eroglu, Cagla and Goebbels, Sandra and Kaeser, Pascal S. and Kay, Jeremy N. and Lu, Wei and Luo, Liqun and Mandai, Kenji and McBain, Chris J. and Nave, Klaus-Armin and Prado, Marco A. M. and Prado, Vania F. and Rothstein, Jeffrey and Rubenstein, John L. R. and Saher, Gesine and Sakimura, Kenji and Sanes, Joshua R. and Scheiffele, Peter and Takai, Yoshimi and Umemori, Hisashi and Verhage, Matthijs and Yuzaki, Michisuke and Zoghbi, Huda Yahya and Kawabe, Hiroshi and Craig, Ann Marie. (2020) Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors. Neuron, 106 (1). pp. 37-65.e5.

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Official URL: https://edoc.unibas.ch/75874/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele)
UniBasel Contributors:Scheiffele, Peter
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 Nov 2021 16:39
Deposited On:23 Nov 2021 16:39

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