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De novo missense and protein-truncating variants from exome sequencing studies have directly implicated <jats:italic>MBD5<\/jats:italic> in the etiology of autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDDs). However, little is known concerning the specific function(s) of MBD5.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To gain insight into the complex interactions associated with alteration of <jats:italic>MBD5<\/jats:italic> in individuals with ASD and related NDDs, we explored the transcriptional landscape of <jats:italic>MBD5<\/jats:italic> haploinsufficiency across multiple mouse brain regions of a heterozygous hypomorphic <jats:italic>Mbd5<\/jats:italic><jats:sup>+\/GT<\/jats:sup> mouse model, and compared these results to CRISPR-mediated mutations of <jats:italic>MBD5<\/jats:italic> in human iPSC-derived neuronal models.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Gene expression analyses across three brain regions from <jats:italic>Mbd5<\/jats:italic><jats:sup>+\/GT<\/jats:sup> mice showed subtle transcriptional changes, with cortex displaying the most widespread changes following <jats:italic>Mbd5<\/jats:italic> reduction, indicating context-dependent effects. Comparison with <jats:italic>MBD5<\/jats:italic> reduction in human neuronal cells reinforced the context-dependence of gene expression changes due to MBD5 deficiency. Gene co-expression network analyses revealed gene clusters that were associated with reduced <jats:italic>MBD5<\/jats:italic> expression and enriched for terms related to ciliary function.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Limitations<\/jats:title>\n                <jats:p>These analyses included a limited number of mouse brain regions and neuronal models, and the effects of the gene knockdown are subtle. As such, these results will not reflect the full extent of <jats:italic>MBD5<\/jats:italic> disruption across human brain regions during early neurodevelopment in ASD, or capture the diverse spectrum of cell-type-specific changes associated with <jats:italic>MBD5<\/jats:italic> alterations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study points to modest and context-dependent transcriptional consequences of <jats:italic>Mbd5<\/jats:italic> disruption in the brain. It also suggests a possible link between <jats:italic>MBD5<\/jats:italic> and perturbations in ciliary function, which is an established pathogenic mechanism in developmental disorders and syndromes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13229-020-00354-1","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T15:03:44Z","timestamp":1591369424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons"],"prefix":"10.1186","volume":"11","author":[{"given":"Catarina M.","family":"Seabra","sequence":"first","affiliation":[]},{"given":"Tatsiana","family":"Aneichyk","sequence":"additional","affiliation":[]},{"given":"Serkan","family":"Erdin","sequence":"additional","affiliation":[]},{"given":"Derek J. 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