@article{SchrautJakobWeidneretal.2014, author = {Schraut, K. G. and Jakob, S. B. and Weidner, M. T. and Schmitt, A. G. and Scholz, C. J. and Strekalova, T. and El Hajj, N. and Eijssen, L. M. T. and Domschke, K. and Reif, A. and Haaf, T. and Ortega, G. and Steinbusch, H. W. M. and Lesch, K. P. and Van den Hove, D. L.}, title = {Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice}, series = {Translational Psychiatry}, volume = {4}, journal = {Translational Psychiatry}, doi = {10.1038/tp.2014.107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119199}, pages = {e473}, year = {2014}, abstract = {The serotonin transporter gene (5-HTT/SLC6A4)-linked polymorphic region has been suggested to have a modulatory role in mediating effects of early-life stress exposure on psychopathology rendering carriers of the low-expression short (s)-variant more vulnerable to environmental adversity in later life. The underlying molecular mechanisms of this gene-by-environment interaction are not well understood, but epigenetic regulation including differential DNA methylation has been postulated to have a critical role. Recently, we used a maternal restraint stress paradigm of prenatal stress (PS) in 5-HTT-deficient mice and showed that the effects on behavior and gene expression were particularly marked in the hippocampus of female 5-Htt+/- offspring. Here, we examined to which extent these effects are mediated by differential methylation of DNA. For this purpose, we performed a genome-wide hippocampal DNA methylation screening using methylated-DNA immunoprecipitation (MeDIP) on Affymetrix GeneChip Mouse Promoter 1.0 R arrays. Using hippocampal DNA from the same mice as assessed before enabled us to correlate gene-specific DNA methylation, mRNA expression and behavior. We found that 5-Htt genotype, PS and their interaction differentially affected the DNA methylation signature of numerous genes, a subset of which showed overlap with the expression profiles of the corresponding transcripts. For example, a differentially methylated region in the gene encoding myelin basic protein (Mbp) was associated with its expression in a 5-Htt-, PS- and 5-Htt × PS-dependent manner. Subsequent fine-mapping of this Mbp locus linked the methylation status of two specific CpG sites to Mbp expression and anxiety-related behavior. In conclusion, hippocampal DNA methylation patterns and expression profiles of female prenatally stressed 5-Htt+/- mice suggest that distinct molecular mechanisms, some of which are promoter methylation-dependent, contribute to the behavioral effects of the 5-Htt genotype, PS exposure and their interaction.}, language = {en} } @article{JanschGuentherWaideretal.2018, author = {Jansch, Charline and G{\"u}nther, Katharina and Waider, Jonas and Ziegler, Georg C. and Forero, Andrea and Kollert, Sina and Svirin, Evgeniy and P{\"u}hringer, Dirk and Kwok, Chee Keong and Ullmann, Reinhard and Maierhofer, Anna and Flunkert, Julia and Haaf, Thomas and Edenhofer, Frank and Lesch, Klaus-Peter}, title = {Generation of a human induced pluripotent stem cell (iPSC) line from a 51-year-old female with attention-deficit/hyperactivity disorder (ADHD) carrying a duplication of SLC2A3}, series = {Stem Cell Research}, volume = {28}, journal = {Stem Cell Research}, doi = {10.1016/j.scr.2018.02.005}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176654}, pages = {136-140}, year = {2018}, abstract = {Fibroblasts were isolated from a skin biopsy of a clinically diagnosed 51-year-old female attention-deficit/hyperactivity disorder (ADHD) patient carrying a duplication of SLC2A3, a gene encoding neuronal glucose transporter-3 (GLUT3). Patient fibroblasts were infected with Sendai virus, a single-stranded RNA virus, to generate transgene-free human induced pluripotent stem cells (iPSCs). SLC2A3-D2-iPSCs showed expression of pluripotency-associated markers, were able to differentiate into cells of the three germ layers in vitro and had a normal female karyotype. This in vitro cellular model can be used to study the role of risk genes in the pathogenesis of ADHD, in a patient-specific manner.}, language = {en} }