Modelling genetic mosaicism of neurodevelopmental disorders in vivo by a Cre-amplifying fluorescent reporter.
Action Potentials
Animals
Animals, Newborn
Disease Models, Animal
Electroencephalography
Fluorescent Dyes
/ chemistry
Gene Expression
Genes, Reporter
HEK293 Cells
Humans
Integrases
/ metabolism
Mice
Mice, Inbred C57BL
Mosaicism
NIH 3T3 Cells
Neurodevelopmental Disorders
/ genetics
PTEN Phosphohydrolase
/ metabolism
Tamoxifen
/ pharmacology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 12 2020
03 12 2020
Historique:
received:
29
01
2020
accepted:
27
10
2020
entrez:
4
12
2020
pubmed:
5
12
2020
medline:
17
12
2020
Statut:
epublish
Résumé
Genetic mosaicism, a condition in which an organ includes cells with different genotypes, is frequently present in monogenic diseases of the central nervous system caused by the random inactivation of the X-chromosome, in the case of X-linked pathologies, or by somatic mutations affecting a subset of neurons. The comprehension of the mechanisms of these diseases and of the cell-autonomous effects of specific mutations requires the generation of sparse mosaic models, in which the genotype of each neuron is univocally identified by the expression of a fluorescent protein in vivo. Here, we show a dual-color reporter system that, when expressed in a floxed mouse line for a target gene, leads to the creation of mosaics with tunable degree. We demonstrate the generation of a knockout mosaic of the autism/epilepsy related gene PTEN in which the genotype of each neuron is reliably identified, and the neuronal phenotype is accurately characterized by two-photon microscopy.
Identifiants
pubmed: 33273479
doi: 10.1038/s41467-020-19864-w
pii: 10.1038/s41467-020-19864-w
pmc: PMC7713426
doi:
Substances chimiques
Fluorescent Dyes
0
Tamoxifen
094ZI81Y45
Cre recombinase
EC 2.7.7.-
Integrases
EC 2.7.7.-
PTEN Phosphohydrolase
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6194Références
Nat Med. 2015 Apr;21(4):395-400
pubmed: 25799227
Brain. 2017 Oct 1;140(10):2610-2622
pubmed: 28969385
Neuron. 2012 Apr 12;74(1):41-8
pubmed: 22500628
Am J Hum Genet. 2000 Sep;67(3):574-81
pubmed: 10915612
Epilepsia. 2015 Nov;56(11):1669-86
pubmed: 26434565
Epilepsia. 2016 Mar;57(3):e51-5
pubmed: 26765483
Trends Genet. 2018 May;34(5):333-340
pubmed: 29336844
J Neurosci. 2019 Apr 3;39(14):2762-2773
pubmed: 30700531
Nat Commun. 2019 May 22;10(1):2262
pubmed: 31118412
Nature. 2000 Apr 20;404(6780):876-81
pubmed: 10786794
Nat Med. 2015 Dec;21(12):1445-54
pubmed: 26523971
Biomed Opt Express. 2016 Mar 30;7(4):1604-13
pubmed: 27446677
Nat Neurosci. 2017 Sep;20(9):1217-1224
pubmed: 28714951
Ann Neurol. 1995 Apr;37(4):476-87
pubmed: 7717684
Am J Hum Genet. 2017 Sep 7;101(3):369-390
pubmed: 28867142
Biochemistry. 2003 Jul 8;42(26):7879-84
pubmed: 12834339
Epilepsy Res. 2015 Jul;113:132-9
pubmed: 25986200
J Neurosci. 2011 Mar 16;31(11):4345-54
pubmed: 21411674
Elife. 2017 May 16;6:
pubmed: 28509666
Development. 2011 Dec;138(23):5049-55
pubmed: 22069183
Nat Commun. 2016 Jun 01;7:11753
pubmed: 27249187
Brain. 2000 Aug;123 ( Pt 8):1733-51
pubmed: 10908202
Dis Model Mech. 2009 Jul-Aug;2(7-8):389-98
pubmed: 19470613
Nat Rev Neurol. 2011 Jul 05;7(8):439-50
pubmed: 21727940
Genesis. 2013 Jun;51(6):436-42
pubmed: 23441020
Sci Rep. 2017 Jan 10;7:40054
pubmed: 28071688
Nat Methods. 2018 Dec;15(12):1033-1036
pubmed: 30455464
Nat Genet. 2012 Jun 24;44(8):941-5
pubmed: 22729223
BMC Med Genet. 2014 Feb 27;15:26
pubmed: 24580998
Dev Neurosci. 2008;30(1-3):59-64
pubmed: 18075255
Cell Rep. 2012 Aug 30;2(2):386-96
pubmed: 22884371
Epilepsia. 2011 Jan;52(1):158-74
pubmed: 21219302
Nat Rev Genet. 2013 May;14(5):307-20
pubmed: 23594909
Development. 2015 Oct 15;142(20):3601-11
pubmed: 26400094
Brain. 2015 Jun;138(Pt 6):1613-28
pubmed: 25722288
Nat Genet. 2008 Jun;40(6):776-81
pubmed: 18469813
Mol Psychiatry. 2019 Nov;24(11):1627-1640
pubmed: 30967683
BMC Med Genet. 2018 Jun 4;19(1):92
pubmed: 29866057
Genesis. 2002 Nov;34(3):208-14
pubmed: 12395386
Nat Genet. 2001 Dec;29(4):404-11
pubmed: 11726927
Front Mol Neurosci. 2014 Apr 01;7:23
pubmed: 24744697
Sci Rep. 2011;1:45
pubmed: 22355564
Nat Commun. 2012 Jul 17;3:960
pubmed: 22805567
Neuron. 2012 Sep 20;75(6):1022-34
pubmed: 22998871
PLoS Genet. 2009 Feb;5(2):e1000381
pubmed: 19214208
PLoS Genet. 2016 Sep 15;12(9):e1006245
pubmed: 27632392
Nat Genet. 2001 Dec;29(4):396-403
pubmed: 11726926
Nat Rev Genet. 2017 Feb;18(2):128-142
pubmed: 27941868
Mol Syndromol. 2016 Sep;7(4):220-233
pubmed: 27781032
Cell. 2019 Sep 19;179(1):251-267.e24
pubmed: 31539496
Sci Rep. 2018 Apr 12;8(1):5913
pubmed: 29651133
Nat Commun. 2019 Nov 19;10(1):5224
pubmed: 31745093
Nat Protoc. 2016 Mar;11(3):399-412
pubmed: 26844428
Front Neural Circuits. 2012 Jul 27;6:47
pubmed: 22866029
Neurology. 2003 Oct 28;61(8):1042-6
pubmed: 14581661
J Vis Exp. 2013 Feb 11;(72):
pubmed: 23426329
Trends Neurosci. 2010 Feb;33(2):67-75
pubmed: 19963289
Nat Neurosci. 2018 Nov;21(11):1504-1514
pubmed: 30349109
J Neurosci. 2015 Jan 21;35(3):943-59
pubmed: 25609613
Cell. 2017 Aug 10;170(4):800-814.e18
pubmed: 28802047
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):1027-32
pubmed: 17209010
Nat Biotechnol. 2003 May;21(5):562-5
pubmed: 12665802
Hum Mutat. 2017 Aug;38(8):1002-1013
pubmed: 28503910
N Engl J Med. 2014 Aug 21;371(8):733-43
pubmed: 25140959
Brain Res. 2007 Sep 7;1168:112-23
pubmed: 17706614
Neuron. 2013 Jun 5;78(5):773-84
pubmed: 23764283
J Vis Exp. 2017 Nov 17;(129):
pubmed: 29286375
Brain. 2004 Nov;127(Pt 11):2406-18
pubmed: 15319274