Experimental models of Rett syndrome based on Mecp2 dysfunction.
Rett syndrome (RTT) is a neurodevelopmental disorder predominantly occurring in females with an incidence of 1:10,000 births and caused by sporadic mutations in the MECP2 gene, which encodes methyl-CpG-binding protein-2, an epigenetic transcription factor that binds methylated DNA. The clinical hallmarks include a period of apparently normal early development followed by a plateau and then subsequent frank regression. Impaired visual and aural contact often lead to an initial diagnosis of autism. The characterization of experimental models based on the loss-of-function of the mouse Mecp2 gene revealed that subtle changes in the morphology and function of brain cells and synapses have profound consequences on network activities that underlie critical brain functions. Furthermore, these experimental models have been used for successful reversals of RTT-like symptoms by genetic, pharmacological and environmental manipulations, raising hope for novel therapeutic strategies to improve the quality of life of RTT individuals.
Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Gaston
G
Calfa
Alan K
AK
Percy
Lucas
L
Pozzo-Miller
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009474:Neurons / Q000502:physiology; D015518:Rett Syndrome / Q000209:etiology* / Q000235:genetics; D013569:Synapses / Q000502:physiology
C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2
J Neuropathol Exp Neurol. 1998 Nov;57(11):1013-7
9825937
Hum Mol Genet. 2007 Mar 15;16(6):640-50
17309881
Ann Neurol. 2008 Apr;63(4):444-53
18389497
J Neurosci. 2008 May 21;28(21):5422-32
18495876
J Neurosci. 2009 Apr 1;29(13):4218-27
19339616
PLoS One. 2010 Jul 02;5(7):e11399
20625482
Neuron. 2002 Jul 18;35(2):243-54
12160743
Neurobiol Dis. 2007 Jul;27(1):77-89
17532643
Front Synaptic Neurosci. 2010 Aug 06;2:28
21423514
Neuropediatrics. 1995 Apr;26(2):105-8
7566446
Neuron. 2004 Sep 30;44(1):5-21
15450156
Neuroreport. 1994 Jul 21;5(12):1509-13
7948850
Eur J Hum Genet. 2001 Mar;9(3):231-6
11313764
Neurobiol Dis. 2009 Apr;34(1):71-7
19167498
Wien Med Wochenschr. 1966 Sep 10;116(37):723-6
5300597
Int Rev Neurobiol. 2009;89:147-60
19900619
BMC Neurosci. 2010 Feb 17;11:19
20163734
Neurobiol Dis. 2007 May;26(2):473-80
17395475
J Med Genet. 2003 Jul;40(7):487-93
12843318
Science. 2008 May 30;320(5880):1224-9
18511691
Mol Cell Neurosci. 2004 Sep;27(1):44-58
15345242
Mol Cell Neurosci. 2009 Nov;42(3):243-54
19628041
Mol Endocrinol. 2001 Oct;15(10):1748-57
11579207
J Neurosci. 2009 Oct 7;29(40):12440-8
19812320
Neuron. 2004 Jun 24;42(6):947-59
15207239
Behav Pharmacol. 2008 Sep;19(5-6):501-17
18690105
J Neurosci Methods. 1995 Mar;57(1):55-61
7791365
J Neurosci. 2009 Jun 10;29(23):7395-403
19515907
Ment Retard Dev Disabil Res Rev. 2002;8(2):72-6
12112730
Neuropediatrics. 1995 Apr;26(2):109-13
7566447
J Neurosci Res. 2010 May 15;88(7):1500-9
19998492
Brain. 2006 Apr;129(Pt 4):887-98
16467389
Cell. 2005 Nov 4;123(3):493-505
16269339
J Med Genet. 2006 May;43(5):451-6
16183801
J Biol Chem. 2008 Jul 18;283(29):20523-34
18499664
J Comp Neurol. 2009 May 20;514(3):240-58
19296534
Neurology. 2008 Apr 15;70(16):1313-21
18337588
J Neurosci. 2009 Apr 22;29(16):5051-61
19386901
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2169-74
18250306
Brain Res. 2008 Oct 27;1237:101-9
18778693
Hum Mol Genet. 2008 Jun 15;17(12):1718-27
18321864
Am J Med Genet A. 2010 May;152A(5):1079-88
20425814
Annu Rev Neurosci. 1989;12:13-31
2648947
Genet Med. 2006 Dec;8(12):784-92
17172942
Neuron. 2007 Dec 20;56(6):955-62
18093519
Cell. 1997 Feb 21;88(4):471-81
9038338
Science. 1974 Dec 20;186(4169):1126-8
4469701
J Neurochem. 2009 Jan;108(2):361-71
19012748
Mol Cell. 2008 Feb 29;29(4):525-31
18313390
J Neuropathol Exp Neurol. 1995 Mar;54(2):195-201
7876888
J Child Neurol. 2005 Sep;20(9):747-53
16225830
Am J Hum Genet. 2004 Mar;74(3):511-20
14973779
Brain Dev. 2001 Dec;23 Suppl 1:S165-73
11738866
Curr Biol. 2005 Nov 8;15(21):1961-7
16271875
Hum Mol Genet. 2004 Nov 1;13(21):2679-89
15351775
Nature. 2001 May 24;411(6836):494-8
11373684
Behav Brain Res. 2009 Jan 3;196(1):44-8
18687363
J Neurosci. 2010 Apr 14;30(15):5303-10
20392952
Novartis Found Symp. 1998;214:6-16; discussion 16-21, 46-50
9601009
Cereb Cortex. 2000 Oct;10(10):981-91
11007549
Neuroscience. 2010 Feb 17;165(4):1254-60
19932741
J Neurochem. 2004 May;89(4):844-52
15140184
J Neurosci. 2000 Jan 1;20(1):8-21
10627576
Neuron. 2008 Dec 26;60(6):950-60
19109903
Brain Res. 2007 Nov 14;1180:1-6
17936729
Biochem Soc Trans. 2010 Apr;38(2):498-506
20298210
Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21966-71
20007372
Pediatrics. 2006 Dec;118(6):e1687-95
17088400
J Neuropathol Exp Neurol. 2005 Jun;64(6):537-44
15977646
Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7834-8
1679238
Nat Genet. 2001 Mar;27(3):322-6
11242117
Ann Neurol. 1999 Apr;45(4):541-5
10211484
Neuron. 2007 Nov 8;56(3):422-37
17988628
Neuron. 1999 Oct;24(2):401-14
10571233
Nucleic Acids Res. 1995 Dec 25;23(24):5080-1
8559668
Am J Hum Genet. 2001 May;68(5):1093-101
11309679
Biol Psychiatry. 2010 Apr 1;67(7):657-65
20172507
J Neurosci. 2006 Oct 18;26(42):10911-5
17050729
J Neurophysiol. 2010 May;103(5):2470-81
20200124
Neuron. 1996 Jun;16(6):1197-207
8663996
Cereb Cortex. 2000 Oct;10(10):992-1004
11007550
Nat Rev Neurosci. 2000 Dec;1(3):191-8
11257907
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2029-34
19208815
Curr Biol. 2006 Apr 4;16(7):710-6
16581518
Science. 2003 Oct 31;302(5646):890-3
14593184
Neuroscience. 2006;139(4):1449-60
16549272
Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12560-5
16116096
Nat Genet. 1999 Oct;23(2):185-8
10508514
Nat Genet. 1996 Feb;12(2):205-8
8563762
J Neurobiol. 2003 Apr;55(1):86-96
12605461
Neuron. 2006 Oct 19;52(2):255-69
17046689
Neurobiol Dis. 2005 Jun-Jul;19(1-2):18-27
15837557
Nat Med. 2008 Aug;14(8):843-8
18568033
Ann Neurol. 2003 Aug;54(2):206-18
12891673
Science. 2003 Oct 31;302(5646):885-9
14593183
Neuron. 2008 Sep 25;59(6):947-58
18817733
Ann Neurol. 1983 Oct;14(4):471-9
6638958
Eur J Neurosci. 2008 Jun;27(12):3342-50
18557922
Eur J Neurosci. 2007 Apr;25(7):1915-22
17439480
J Neurophysiol. 2008 Jan;99(1):112-21
18032561
Nat Rev Neurosci. 2001 Jan;2(1):24-32
11253356
Mol Cell Biol. 1998 Nov;18(11):6538-47
9774669
J Comp Neurol. 2007 Apr 1;501(4):526-42
17278130
Ann Neurol. 1993 Aug;34(2):227-34
8338347
Brain Dev. 1985;7(3):372-3
4061772
Am J Hum Genet. 2002 Apr;70(4):1034-7
11885030
Hum Mol Genet. 2008 May 15;17(10):1386-96
18223199
Neurology. 1995 Aug;45(8):1581-6
7644058
Neurobiol Dis. 2006 Jan;21(1):217-27
16087343
Neuron. 2006 Feb 2;49(3):341-8
16446138
Neurobiol Dis. 2008 Jul;31(1):110-9
18571096
Neurobiol Dis. 2009 Aug;35(2):219-33
19442733
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6033-8
15069197
Nat Genet. 1999 Sep;23(1):99-103
10471508
Neurology. 2006 Jul 11;67(1):164-6
16832102
Hum Mol Genet. 2007 Oct 1;16(19):2315-25
17635839
Brain Dev. 1997 Jan;19(1):25-34
9071487
J Pediatr. 2006 Mar;148(3):347-52
16615965
Hum Mol Genet. 2004 Jun 15;13(12):1275-86
15115765
Hippocampus. 2008;18(3):294-309
18058824
Nat Neurosci. 2007 Apr;10(4):411-3
17322876
Learn Mem. 2003 Mar-Apr;10(2):86-98
12663747
Learn Mem. 2002 Sep-Oct;9(5):224-37
12359832
Int J Dev Neurosci. 2008 Aug;26(5):457-65
18396005
Nature. 2007 May 3;447(7140):87-91
17450125
Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17551-8
16251272
Neuroscience. 2007 May 25;146(3):907-21
17383101
Nucleic Acids Res. 1993 Oct 25;21(21):4886-92
8177735
Neurobiol Dis. 2009 May;34(2):199-211
19217433
J Neurosci. 2009 Sep 30;29(39):12187-95
19793977
Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2709-14
17296936
Science. 2007 Feb 23;315(5815):1143-7
17289941
Science. 1999 Oct 29;286(5441):950-2
10542148
Nat Rev Neurosci. 2006 Sep;7(9):697-709
16924259
J Child Neurol. 1999 Aug;14(8):524-8
10456763
Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1931-6
17267601
Trends Neurosci. 2006 Oct;29(10):554-62
16890999
J Child Neurol. 2007 Dec;22(12):1338-41
18174548
Genesis. 2004 Oct;40(2):67-73
15452869
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16472-7
16251278
Biol Psychiatry. 2006 Mar 1;59(5):468-76
16199017
J Neurosci. 2007 Oct 3;27(40):10912-7
17913925
Nature. 1993 Dec 9;366(6455):569-72
7902955
Neuron. 2007 Oct 4;56(1):58-65
17920015
J Neurosci. 2006 Jan 4;26(1):319-27
16399702
J Neurosci. 2010 Apr 14;30(15):5346-56
20392956
J Neurosci. 2009 Sep 9;29(36):11263-70
19741133
Nature. 2002 Jan 31;415(6871):526-30
11793011
Brain Res Brain Res Rev. 2002 Jun;39(1):29-54
12086707
Mol Cell Neurosci. 2004 Nov;27(3):306-21
15519245
Mamm Genome. 2000 Mar;11(3):182-90
10723722
Cell. 1992 Jun 12;69(6):905-14
1606614
Neurology. 2008 Mar 11;70(11):868-75
18332345
J Appl Physiol (1985). 2008 Jan;104(1):198-204
18006868
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10518-22
12930888
Neurobiol Dis. 2010 Apr;38(1):8-16
20045053
Nat Genet. 2001 Mar;27(3):327-31
11242118
Acta Neuropathol. 1988;76(2):142-58
2900587
J Neurodev Disord. 2009 Sep;1(3):185-96
19966931
Nat Neurosci. 2007 Mar;10(3):280-2
17259980
Methods. 1998 Apr;14(4):381-92
9608509
J Neurobiol. 1999 Oct;41(1):108-18
10504198
J Med Genet. 2005 Feb;42(2):e12
15689435
Nat Neurosci. 2009 Mar;12(3):311-7
19234456
Neurology. 2010 Mar 16;74(11):909-12
20231667
Nucleic Acids Res. 2004 Mar 19;32(5):1818-23
15034150
Neurosci Lett. 2008 Mar 5;433(1):22-7
18226451
Nat Genet. 2004 Apr;36(4):339-41
15034579
Exp Neurol. 1999 Apr;156(2):345-52
10328941
Nat Methods. 2009 May;6(5):370-6
19404254