title: Expression of mutant human DISC1 in mice supports abnormalities in differentiation of oligodendrocytes.
abstract: Abnormalities in oligodendrocyte (OLG) differentiation and OLG gene expression deficit have been described in schizophrenia (SZ). Recent studies revealed a critical requirement for Disrupted-in-Schizophrenia 1 (DISC1) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (ΔhDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of ΔhDISC1 may influence the development of OLGs in this mouse model. OLG- and cell cycle-associated gene and protein expression were characterized in the forebrain of ΔhDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood. The results suggest that the expression of ΔhDISC1 exerts a significant influence on oligodendrocyte differentiation and function, evidenced by premature OLG differentiation and increased proliferation of their progenitors. Additional findings showed that neuregulin 1 and its receptors may be contributing factors to the observed upregulation of OLG genes. Thus, OLG function may be perturbed by mutant hDISC1 in a model system that provides new avenues for studying aspects of the pathogenesis of SZ.
authors: Department of Psychiatry, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6575, USA. pavel.katsel@mssm.edu
authors: Pavel
authors: P
authors: Katsel
authors: Weilun
authors: W
authors: Tan
authors: Bagrat
authors: B
authors: Abazyan
authors: Kenneth L
authors: KL
authors: Davis
authors: Christopher
authors: C
authors: Ross
authors: Mikhail V
authors: MV
authors: Pletnikov
authors: Vahram
authors: V
authors: Haroutunian
references: Mol Psychiatry. 2009 Sep;14(9):865-73
references: 18317464
references: Mol Psychiatry. 2004 Dec;9(12):1100-10
references: 15381924
references: Neuron. 1994 Jun;12(6):1363-75
references: 8011341
references: Am J Psychiatry. 2004 May;161(5):882-8
references: 15121654
references: Genes Dev. 2002 Jan 15;16(2):165-70
references: 11799060
references: Mol Cell Neurosci. 1997;8(5):311-22
references: 9073394
references: Development. 1999 Sep;126(18):4027-37
references: 10457012
references: Gene. 2005 Oct 10;359:119-26
references: 16102918
references: Acta Neuropathol. 1972;20(1):67-77
references: 5020594
references: Nat Rev Neurosci. 2008 Jun;9(6):437-52
references: 18478032
references: J Neurosci. 2005 Jun 1;25(22):5376-81
references: 15930386
references: Lancet. 1990 Jul 7;336(8706):13-6
references: 1973210
references: Mol Psychiatry. 2001 Mar;6(2):173-8
references: 11317219
references: Nat Neurosci. 2008 Dec;11(12):1392-401
references: 18849983
references: Mol Psychiatry. 2008 Feb;13(2):173-86, 115
references: 17848917
references: Arch Gen Psychiatry. 1999 Apr;56(4):367-74
references: 10197834
references: Schizophr Res. 2007 Aug;94(1-3):273-80
references: 17566708
references: J Neurosci Res. 2004 Sep 15;77(6):858-66
references: 15334603
references: Schizophr Res. 2010 Jul;120(1-3):150-8
references: 20580881
references: Mol Psychiatry. 2011 Mar;16(3):293-306
references: 20048751
references: Biol Psychiatry. 2003 Jun 15;53(12):1075-85
references: 12814859
references: Schizophr Res. 2002 Oct 1;57(2-3):127-38
references: 12223243
references: Neuron. 2004 Oct 14;44(2):251-61
references: 15473965
references: Am J Hum Genet. 2001 Aug;69(2):428-33
references: 11443544
references: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7482-7
references: 16641098
references: Neuron. 2005 Sep 1;47(5):681-94
references: 16129398
references: Hum Mol Genet. 2009 Feb 1;18(3):391-404
references: 18996920
references: Brain Res Bull. 2001 Jul 15;55(5):597-610
references: 11576756
references: J Neurosci Res. 2005 Mar 15;79(6):868-78
references: 15696539
references: Development. 1993 Feb;117(2):525-33
references: 8330523
references: Neuroreport. 1998 Feb 16;9(3):425-30
references: 9512384
references: Biol Psychiatry. 2003 Mar 1;53(5):412-21
references: 12614994
references: J Psychiatr Res. 2010 Feb;44(3):149-56
references: 19699489
references: Neurobiol Dis. 2006 Mar;21(3):531-40
references: 16213148
references: J Neurosci Res. 2002 Aug 15;69(4):488-96
references: 12210842
references: Bioessays. 2000 Nov;22(11):987-96
references: 11056475
references: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14501-6
references: 17675407
references: Trends Biochem Sci. 1998 Jul;23(7):247-51
references: 9697414
references: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4746-51
references: 11296301
references: Psychiatr Genet. 2001 Jun;11(2):71-8
references: 11525420
references: Development. 2009 Aug;136(15):2623-32
references: 19570850
references: J Neurol Neurosurg Psychiatry. 2000 Jan;68(1):70-4
references: 10601405
references: Mol Psychiatry. 2003 Sep;8(9):811-20
references: 12931208
references: Schizophr Res. 2009 Jul;112(1-3):54-64
references: 19447584
references: Nature. 2010 Nov 11;468(7321):244-52
references: 21068833
references: Brain. 2001 May;124(Pt 5):882-92
references: 11335691
references: Schizophr Res. 2004 Apr 1;67(2-3):269-75
references: 14984887
references: Schizophr Res. 2005 Nov 15;79(2-3):157-73
references: 16139990
references: Neuron. 2008 Aug 28;59(4):581-95
references: 18760695
references: Schizophr Res. 2005 Sep 15;77(2-3):241-52
references: 15923110
references: Neurosci Lett. 2005 Jun 24;381(3):223-7
references: 15896474
references: Neuron. 2007 May 3;54(3):387-402
references: 17481393
references: Science. 2004 Apr 30;304(5671):700-3
references: 15044753
references: J Neurosci Res. 2002 Jan 1;67(1):100-5
references: 11754085
references: Ment Retard Dev Disabil Res Rev. 2006;12(2):85-96
references: 16807909
references: Cell. 2004 Aug 20;118(4):477-91
references: 15315760
references: Cell. 2009 Mar 20;136(6):1017-31
references: 19303846
references: Mol Psychiatry. 2004 Dec;9(12):1083-90
references: 15249933
references: Lancet. 2003 Sep 6;362(9386):798-805
references: 13678875
references: Neuropsychopharmacology. 2008 Nov;33(12):2993-3009
references: 18322470
references: Gene Expr Patterns. 2008 Sep;8(7-8):494-501
references: 18620078
references: Novartis Found Symp. 2001;237:100-7; discussion 107-12, 158-63
references: 11444039
references: Cell. 2006 Apr 7;125(1):127-42
references: 16615895
references: Nat Neurosci. 2009 Apr;12(4):418-27
references: 19270689
references: Development. 2001 Jul;128(13):2545-54
references: 11493571
references: J Neurosci. 2008 Oct 22;28(43):10893-904
references: 18945897
references: Glia. 2008 Feb;56(3):284-93
references: 18080294
references: Hum Mol Genet. 2000 May 22;9(9):1415-23
references: 10814723
references: J Neurosci. 2006 Oct 25;26(43):10967-83
references: 17065439
references: Nature. 1988 Dec 22-29;336(6201):738-44
references: 2462672
references: J Neurosci. 2007 Jun 6;27(23):6185-96
references: 17553990
references: Am J Hum Genet. 2002 Oct;71(4):877-92
references: 12145742
references: Brain Res Bull. 2001 Jul 15;55(5):585-95
references: 11576755