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  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., 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.

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Luo, L., Author
Ambrozkiewicz, M.1, Author           
Benseler, F.1, Author           
Chen, C., Author
Dumontier, E., Author
Falkner, S., Author
Furlanis, E., Author
Gomez, A. M., Author
Hoshina, N., Author
Huang, W.-H., Author
Hutchison, M. A., Author
Itoh-Maruoka, Y., Author
Lavery, L. A., Author
Li, W., Author
Maruo, T., Author
Motohashi, J., Author
Pai, E. L.-L., Author
Pelkey, K. A., Author
Pereira, A., Author
Philips, T., Author
Sinclair, J. L., AuthorStogsdill, J. A., AuthorTraunmüller, L., AuthorWang, J., AuthorWortel, J., AuthorYou, W., AuthorAbumaria, N., AuthorBeier, K. T., AuthorBrose, N.1, Author           Burgess, H. A., AuthorCepko, C. L., AuthorCloutier, J.-F., AuthorEroglu, C., AuthorGoebbels, S.2, Author           Kaeser, P. S., AuthorKay, J. N., AuthorLu, W., AuthorLuo, Li., AuthorMandai, K., AuthorMcBain, C. J., AuthorNave, K.-A.3, Author           Prado, M. A.M., AuthorPrado, V. F., AuthorRothstein, J., AuthorRubenstein, John L.R., AuthorSaher, G.3, Author           Sakimura, K., AuthorSanes, J. R., AuthorScheiffele, P., AuthorTakai, Y., AuthorUmemori, H., AuthorVerhage, M., AuthorYuzaki, M., AuthorZoghbi, H. Y., AuthorKawabe, H.1, Author           Craig, A. M., Author more..
1Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173659              
2Developmental neurobiology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173665              
3Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173664              


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 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.


Language(s): eng - English
 Dates: 2020-02-052020-04-20
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.neuron.2020.01.008
 Degree: -



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Project name : Work by Lin Luo and A.M.C. was supported by Canadian Institutes of Health Research (FDN-143206) and Simons Foundation Autism Research Initiative (SFARI 608066). Work by M.C.A. and H.K. was supported by German Research Foundation (DFG) (SPP1365/KA3423/1-1 and KA3423/3-1) and Japan Soci- ety for the Promotion of Science (JSPS) KAKENHI grant number 15K21769.Work by N.B. and F.B. was supported by European Research Council (ERC) Advanced Grant SYNPRIME and the German Research Foundation (DFG) SFB 1286/A9 awards to N.B. Work by C.C., W. Li, and N.A. was supported by the Nat- ural Science Foundation of China grant (81573408), Fudan University-Shanghai Institute of Materia Medica Chinese Academy of Science joint grant (FU- SIMM20174015), and the Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01). Work by J.L.S. and H.A.B. was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Insti- tute of Child Health and Human Development. Work by K.T.B. was supported by National Institutes of Health (NIH) grant F32 DA038913 and NIH grant K99/ R00 DA041445. Work by W.Y. and C.C. was supported by a Howard Hughes Medical Institute (HHMI) salary awarded to C.C. Work by E.D. and J.-F.C. was supported by the Canadian Institutes of Health Research and the Natural Sci- ences and Engineering Research Council of Canada (NSERC). Work by J.A.S. and C.E. was supported by NIH grants RO1DA031833 and F31NS092419. Work by J. Wang and P.S.K. was supported by NIH grants R01NS083898, R01NS103484, and R01MH113349. Work by A.P. and J.N.K. was supported by NIH grants EY024694 to J.N.K. and EY5722 to Duke University. Work by M.A.H. and W. Lu was supported by National Institute of Neurological Disorders and Stroke (NINDS) and NIH Intramural Research Program. Work by W.-H.H. and Liqun Luo was supported by HHMI, SFARI Research Award 345098, and NIH grant R01NS050580 to Liqun Luo and NIH grant 5K99HD092545-02 to W.-H.H. Work by T.M. and K.M. was supported by Japan’s Ministry of Educa- tion, Culture, Sports, Science and Technology KAKENHI grant 16H06463 and JPSP KAKENHI grant 18K06503. Work by K.A.P. and C.J.M. was supported by a Eunice Kennedy Shriver National Institute of Child Health and Human Devel- opment Intramural Award. Work by S.G., G.S., and K.-A.N. was supported by ERC Advanced Grants AxoGLIA and MyeliNANO, the German Research Foun- dation (DFG) (SPP1757), and the Max Planck Society. Work by M.A.M.P. and V.F.P. was supported by Canadian Institute of Health Research grants MOP136930, MOP89919, PJT 162431, and PJT 159781 and NSERC grant 06577-2018 RGPIN. Work by E.L.-L.P. and J.L.R.R. was supported by NIH NINDS grant R01 NS099099, National Institute of Mental Health (NIMH) grant R01 MH081880, and NIMH grant R01 MH049428. Work by J.R.S. was supported by NIH R37NS029169. Work by S.F., E.F., A.M.G., L.T., and P.S. was supported by ERC Advanced Grant SPLICECODE; Swiss National Science Foundation to P.S. and European Molecular Biology Organization EMBO ALTF-70-2015 and aALTF-760-2016 to A.M.G. Work by Y.T. was supported by JPSP KAKENHI grant 26251013. Work by H.U. was supported by NIH R01DA042744, R01MH111647, R01NS092578, and SFARI grants. Work by J. Wortel and M.V. was supported by an ERC Advanced Grant (322966) of the European Union. Work by J.M. and M.Y. was supported by Japan Science and Technology Agency (JPMJCR1854) and KAKENHI (16H06461 and 15H05772). Work by L.A.L. and H.Y.Z. was supported by NIH/NINDS grant 5R01NS057819-13 as well as HHMI to H.Y.Z.
Grant ID : -
Funding program : -
Funding organization : -
Project name : MyeliNANO
Grant ID : 671048
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)
Project name : AxoGLIA
Grant ID : 269020
Funding program : Funding Programme 7 (FP7)
Funding organization : European Commission (EC)
Project name : SYNPRIME
Grant ID : 670283
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

Source 1

Title: Neuron
Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 106 (1) Sequence Number: - Start / End Page: 37 - 65.e5 Identifier: ISSN: 08966273