Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.
Cre-lox
conditional gene targeting
conditional knockin
conditional knockout
conditional reporter
germline recombination
molecular genetics
mosaic recombination
parental sex bias
site-specific recombinase
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
25
07
2019
revised:
12
11
2019
accepted:
10
01
2020
pubmed:
7
2
2020
medline:
29
7
2020
entrez:
7
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32027825
pii: S0896-6273(20)30008-8
doi: 10.1016/j.neuron.2020.01.008
pmc: PMC7377387
mid: NIHMS1607662
pii:
doi:
Substances chimiques
Cre recombinase
EC 2.7.7.-
Integrases
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
37-65.e5Subventions
Organisme : NIDA NIH HHS
ID : R00 DA041445
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY005722
Pays : United States
Organisme : NIDA NIH HHS
ID : F32 DA038913
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY030611
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS057819
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102237
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA031833
Pays : United States
Organisme : NICHD NIH HHS
ID : K99 HD092545
Pays : United States
Organisme : NIMH NIH HHS
ID : R37 MH049428
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103484
Pays : United States
Organisme : NIDA NIH HHS
ID : K99 DA041445
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024694
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS083898
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113349
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA042744
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY012196
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH111647
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS050835
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099099
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH081880
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103555
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS029169
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092578
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH049428
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS092419
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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