A genetic family-based association study of OLIG2 in obsessive-compulsive disorder
ARCHIVES OF GENERAL PSYCHIATRY
Authors: Stewart, S. Evelyn; Platko, Jill; Fagerness, Jesen; Birns, Julie; Jenike, Eric; Smaller, Jordan W.; Perlis, Roy; Leboyer, Marion; Delorme, Richard; Chabane, Nadia; Rauch, Scott L.; Jenike, Michael A.; Pauls, David L.
Abstract
Context: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD. Objectives: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone. Design: Family-based association candidate gene study. Setting: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics. Participants: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD. Main Outcome Measures: Genotypes of single nucleotide polymorphism markers and related haplotypes. Results: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P <.001), rs1059004 (minor allele frequency, 44%; P=.005), and rs9653711 (minor allele frequency, 44%; P=.004). A 5-marker haplotype (A/C/T/ T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008). Conclusions: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder.
New mouse oligodendrocyte precursor (mOP) cells for studies on oligodendrocyte maturation and function
JOURNAL OF NEUROSCIENCE METHODS
Authors: Lin, Tong; Xiang, Zhongmin; Cui, Libin; Stallcup, William; Reeves, Steven A.
Abstract
Oligodendrocyte precursor (OP) cells give rise to mature oligodendrocytes (OL), which are necessary for myelination of axons during CNS development and following damage to the myelin sheath that occurs in demyelinating diseases. To facilitate studies designed to understand OP maturation and OL function, we have developed OP cells that can be grown continuously, expanded, and differentiated into mature OLs. Cultures of late passage mOP cells grown in proliferation medium are highly pure early stage oligodendrocyte precursors where > 90% assume a characteristic bipolar morphology. Immunocytochemical analysis using antibodies that recognize progressive stages of OP maturation (A2B5, NG2, GD3 and O4) confirmed that mOP cells have a stable early stage OP cell phenotype. In addition, mOP cells can be induced to differentiate into mature forms of oligodendrocytes in vitro and in vivo, as characterized morphologically by the presence of multiple processes with secondary and tertiary branches, and by immunostaining and quantitative real-time PCR for the mature oligodendrocyte markers MBP, MAG, PLP, and MOBP. Finally, differentiation of mOP cells was accompanied by up-regulation of mRNA encoding Olig2 but not Olig1, which is consistent with previous findings showing that Olig2 is necessary for specification of oligodendrocytes. These new mOP cells should significantly benefit in vitro and in vivo studies on OP maturation and function. (c) 2006 Elsevier B.V. All rights reserved.