Optimizing nervous system-specific gene targeting with Cre driver lines: 
prevalence of germline recombination and influencing factors

Luo, L.; Ambrozkiewicz, M.; Benseler, F.; Chen, C.; Dumontier, E.; Falkner, S.; Furlanis, E.; Gomez, A. M.; Hoshina, N.; Huang, W.-H.; Hutchison, M. A.; Itoh-Maruoka, Y.; Lavery, L. A.; Li, W.; Maruo, T.; Motohashi, J.; Pai, E. L.-L.; Pelkey, K. A.; Pereira, A.; Philips, T.; Sinclair, J. L.; Stogsdill, J. A.; Traunmüller, L.; Wang, J.; Wortel, J.; You, W.; Abumaria, N.; Beier, K. T.; Brose, N.; Burgess, H. A.; Cepko, C. L.; Cloutier, J.-F.; Eroglu, C.; Goebbels, S.; Kaeser, P. S.; Kay, J. N.; Lu, W.; Luo, Li.; Mandai, K.; McBain, C. J.; Nave, K.-A.; Prado, M. A.M.; Prado, V. F.; Rothstein, J.; Rubenstein, John L.R.; Saher, G.; Sakimura, K.; Sanes, J. R.; Scheiffele, P.; Takai, Y.; Umemori, H.; Verhage, M.; Yuzaki, M.; Zoghbi, H. Y.; Kawabe, H.; Craig, A. M.

doi:10.1016/j.neuron.2020.01.008

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Optimizing nervous system-specific gene targeting with Cre driver lines: prevalence of germline recombination and influencing factors

MPS-Authors

/persons/resource/persons182069

Ambrozkiewicz, M.
Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182084

Benseler, F.
Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182104

Brose, N.
Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182163

Goebbels, S.
Developmental neurobiology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave, K.-A.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182386

Saher, G.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182236

Kawabe, H.
Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Luo, L., Ambrozkiewicz, M., Benseler, F., Chen, C., Dumontier, E., Falkner, S., et al. (2020). Optimizing nervous system-specific gene targeting with Cre driver lines: prevalence of germline recombination and influencing factors. Neuron, 106(1), 37-65.e5. doi:10.1016/j.neuron.2020.01.008.

Cite as: https://hdl.handle.net/21.11116/0000-0007-4D57-2

Abstract

The Cre-loxP system is invaluable for spatial and
temporal control of gene knockout, knockin, and re-
porter expression in the mouse nervous system.
However, we report varying probabilities of unex-
pected germline recombination in distinct Cre driver
lines designed for nervous system-specific recombi-
nation. 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 expres-
sion in sperm or oocytes. Slight differences among
Cre driver lines utilizing common transcriptional con-
trol elements affect germline recombination rates.
Specific target loci demonstrated differential recom-
bination; 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 pro-
vide guidelines to inform future research for the
neuroscience and broader molecular genetics
communities.