Rapid Generation of Somatic Mouse Mosaics with Locus-Specific, Stably Integrated Transgenic Elements.
Animals
Brain Neoplasms
/ genetics
Cell Line, Tumor
Disease Models, Animal
Female
Gene Targeting
/ methods
Genetic Loci
/ genetics
Glioma
/ genetics
HEK293 Cells
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutagenesis, Insertional
/ methods
Neural Stem Cells
/ metabolism
Recombinases
/ metabolism
Transfection
Transgenes
/ genetics
AAVS1 locus
Brainbow
CRISPR/Cas9 base editors
MADR MAX
RMCE
VCre
ependymoma
epigenetics
scATAC-seq
scRNA-seq
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
19 09 2019
19 09 2019
Historique:
received:
27
09
2018
revised:
24
05
2019
accepted:
06
08
2019
entrez:
21
9
2019
pubmed:
21
9
2019
medline:
9
6
2020
Statut:
ppublish
Résumé
In situ transgenesis methods such as viruses and electroporation can rapidly create somatic transgenic mice but lack control over copy number, zygosity, and locus specificity. Here we establish mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely defined chromosomal loci. We provide a toolkit of MADR elements for combination labeling, inducible and reversible transgene manipulation, VCre recombinase expression, and transgenesis of human cells. Further, we demonstrate the versatility of MADR by creating glioma models with mixed reporter-identified zygosity or with "personalized" driver mutations from pediatric glioma. MADR is extensible to thousands of existing mouse lines, providing a flexible platform to democratize the generation of somatic mosaic mice. VIDEO ABSTRACT.
Identifiants
pubmed: 31539496
pii: S0092-8674(19)30901-8
doi: 10.1016/j.cell.2019.08.013
pmc: PMC6934691
mid: NIHMS1544695
pii:
doi:
Substances chimiques
Recombinases
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
251-267.e24Subventions
Organisme : NINDS NIH HHS
ID : R01 NS089777
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA202900
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM118288
Pays : United States
Organisme : NIBIB NIH HHS
ID : T32 EB009403
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH094589
Pays : United States
Organisme : NINDS NIH HHS
ID : R03 NS101529
Pays : United States
Organisme : NCI NIH HHS
ID : R33 CA236687
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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