--- _id: '691' abstract: - lang: eng text: "Background: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain.\r\n\r\nObjective: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families.\r\n\r\nMethods: Linkage and homozygosity mapping and candidate gene analysis were used to identify homozygous mutations in families. Patient fibroblasts were used to study splicing defect and zebrafish to model the disease.\r\n\r\nResults: We identified six individuals from three unrelated families with a founder homozygous splice mutation in TRAPPC6B, encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features, and showed splicing defect. Zebrafish trappc6b morphants replicated the human phenotype, displaying decreased head size and neuronal hyperexcitability, leading to a lower seizure threshold.\r\n\r\nConclusion: This study provides clinical and functional evidence of the role of TRAPPC6B in brain development and function." article_processing_charge: No article_type: original author: - first_name: Isaac full_name: Marin Valencia, Isaac last_name: Marin Valencia - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Anide full_name: Johansen, Anide last_name: Johansen - first_name: Başak full_name: Rosti, Başak last_name: Rosti - first_name: Mahmoud full_name: Issa, Mahmoud last_name: Issa - first_name: Damir full_name: Musaev, Damir last_name: Musaev - first_name: Gifty full_name: Bhat, Gifty last_name: Bhat - first_name: Eric full_name: Scott, Eric last_name: Scott - first_name: Jennifer full_name: Silhavy, Jennifer last_name: Silhavy - first_name: Valentina full_name: Stanley, Valentina last_name: Stanley - first_name: Rasim full_name: Rosti, Rasim last_name: Rosti - first_name: Jeremy full_name: Gleeson, Jeremy last_name: Gleeson - first_name: Farhad full_name: Imam, Farhad last_name: Imam - first_name: Maha full_name: Zaki, Maha last_name: Zaki - first_name: Joseph full_name: Gleeson, Joseph last_name: Gleeson citation: ama: Marin Valencia I, Novarino G, Johansen A, et al. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 2018;55(1):48-54. doi:10.1136/jmedgenet-2017-104627 apa: Marin Valencia, I., Novarino, G., Johansen, A., Rosti, B., Issa, M., Musaev, D., … Gleeson, J. (2018). A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. BMJ Publishing Group. https://doi.org/10.1136/jmedgenet-2017-104627 chicago: Marin Valencia, Isaac, Gaia Novarino, Anide Johansen, Başak Rosti, Mahmoud Issa, Damir Musaev, Gifty Bhat, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics. BMJ Publishing Group, 2018. https://doi.org/10.1136/jmedgenet-2017-104627. ieee: I. Marin Valencia et al., “A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features,” Journal of Medical Genetics, vol. 55, no. 1. BMJ Publishing Group, pp. 48–54, 2018. ista: Marin Valencia I, Novarino G, Johansen A, Rosti B, Issa M, Musaev D, Bhat G, Scott E, Silhavy J, Stanley V, Rosti R, Gleeson J, Imam F, Zaki M, Gleeson J. 2018. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 55(1), 48–54. mla: Marin Valencia, Isaac, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics, vol. 55, no. 1, BMJ Publishing Group, 2018, pp. 48–54, doi:10.1136/jmedgenet-2017-104627. short: I. Marin Valencia, G. Novarino, A. Johansen, B. Rosti, M. Issa, D. Musaev, G. Bhat, E. Scott, J. Silhavy, V. Stanley, R. Rosti, J. Gleeson, F. Imam, M. Zaki, J. Gleeson, Journal of Medical Genetics 55 (2018) 48–54. date_created: 2018-12-11T11:47:57Z date_published: 2018-01-01T00:00:00Z date_updated: 2023-10-16T09:55:43Z day: '01' department: - _id: GaNo doi: 10.1136/jmedgenet-2017-104627 external_id: isi: - '000418199800007' pmid: - '28626029' intvolume: ' 55' isi: 1 issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056005/ month: '01' oa: 1 oa_version: Submitted Version page: 48 - 54 pmid: 1 project: - _id: 254BA948-B435-11E9-9278-68D0E5697425 grant_number: '401299' name: Probing development and reversibility of autism spectrum disorders publication: Journal of Medical Genetics publication_identifier: issn: - 0022-2593 publication_status: published publisher: BMJ Publishing Group publist_id: '7016' quality_controlled: '1' scopus_import: '1' status: public title: A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 55 year: '2018' ... --- _id: '395' abstract: - lang: eng text: 'Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. ' acknowledged_ssus: - _id: PreCl - _id: EM-Fac - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Dora-Clara full_name: Tarlungeanu, Dora-Clara id: 2ABCE612-F248-11E8-B48F-1D18A9856A87 last_name: Tarlungeanu citation: ama: Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders . 2018. doi:10.15479/AT:ISTA:th_992 apa: Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992 chicago: Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992. ieee: D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders ,” Institute of Science and Technology Austria, 2018. ista: Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria. mla: Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992. short: D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders , Institute of Science and Technology Austria, 2018. date_created: 2018-12-11T11:46:14Z date_published: 2018-03-01T00:00:00Z date_updated: 2023-09-07T12:38:59Z day: '01' ddc: - '570' - '616' degree_awarded: PhD department: - _id: GaNo doi: 10.15479/AT:ISTA:th_992 file: - access_level: closed checksum: 9f5231c96e0ad945040841a8630232da content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-04-05T09:19:17Z date_updated: 2021-02-11T23:30:15Z embargo_to: open_access file_id: '6217' file_name: 2018_Thesis_Tarlungeanu_source.docx file_size: 43684035 relation: source_file - access_level: open_access checksum: 0c33c370aa2010df5c552db57a6d01e9 content_type: application/pdf creator: dernst date_created: 2019-04-05T09:19:17Z date_updated: 2021-02-11T11:17:16Z embargo: 2018-03-15 file_id: '6218' file_name: 2018_Thesis_Tarlungeanu.pdf file_size: 30511532 relation: main_file file_date_updated: 2021-02-11T23:30:15Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '03' oa: 1 oa_version: Published Version page: '88' project: - _id: 25473368-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: F03523 name: Transmembrane Transporters in Health and Disease publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '7434' pubrep_id: '992' related_material: record: - id: '1183' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 title: 'The branched chain amino acids in autism spectrum disorders ' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2018' ... --- _id: '3' abstract: - lang: eng text: SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder. acknowledged_ssus: - _id: M-Shop - _id: PreCl acknowledgement: This work was supported by the Simons Foundation Autism Research Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N. article_processing_charge: No article_type: original author: - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Niccoló full_name: Arecco, Niccoló last_name: Arecco - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Charles full_name: Girardot, Charles last_name: Girardot - first_name: Eva full_name: Käsper, Eva last_name: Käsper - first_name: Alena full_name: Kozlova, Alena id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D last_name: Kozlova - first_name: Kasumi full_name: Kishi, Kasumi id: 3065DFC4-F248-11E8-B48F-1D18A9856A87 last_name: Kishi - first_name: Ilaria full_name: Chiaradia, Ilaria id: B6467F20-02D0-11E9-BDA5-E960C241894A last_name: Chiaradia orcid: 0000-0002-9529-4464 - first_name: Kyung full_name: Noh, Kyung last_name: Noh - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2 apa: Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2 chicago: Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2. ieee: E. Deliu et al., “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018. ista: Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727. mla: Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2. short: E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727. date_created: 2018-12-11T11:44:05Z date_published: 2018-11-19T00:00:00Z date_updated: 2024-03-27T23:30:44Z day: '19' ddc: - '570' department: - _id: GaNo - _id: EdHa doi: 10.1038/s41593-018-0266-2 external_id: isi: - '000451324700010' file: - access_level: open_access checksum: 60abd0f05b7cdc08a6b0ec460884084f content_type: application/pdf creator: dernst date_created: 2019-04-09T07:41:57Z date_updated: 2020-07-14T12:45:58Z file_id: '6255' file_name: 2017_NatureNeuroscience_Deliu.pdf file_size: 8167169 relation: main_file file_date_updated: 2020-07-14T12:45:58Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '12' language: - iso: eng month: '11' oa: 1 oa_version: Submitted Version page: 1717 - 1727 project: - _id: 254BA948-B435-11E9-9278-68D0E5697425 grant_number: '401299' name: Probing development and reversibility of autism spectrum disorders publication: Nature Neuroscience publication_status: published publisher: Nature Publishing Group publist_id: '8054' pubrep_id: '1071' quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/ record: - id: '6074' relation: popular_science status: public - id: '12364' relation: dissertation_contains status: public scopus_import: '1' status: public title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 21 year: '2018' ... --- _id: '540' abstract: - lang: eng text: RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host. article_number: e1006758 author: - first_name: Kseniya full_name: Khamina, Kseniya last_name: Khamina - first_name: Alexander full_name: Lercher, Alexander last_name: Lercher - first_name: Michael full_name: Caldera, Michael last_name: Caldera - first_name: Christopher full_name: Schliehe, Christopher last_name: Schliehe - first_name: Bojan full_name: Vilagos, Bojan last_name: Vilagos - first_name: Mehmet full_name: Sahin, Mehmet last_name: Sahin - first_name: Lindsay full_name: Kosack, Lindsay last_name: Kosack - first_name: Anannya full_name: Bhattacharya, Anannya last_name: Bhattacharya - first_name: Peter full_name: Májek, Peter last_name: Májek - first_name: Alexey full_name: Stukalov, Alexey last_name: Stukalov - first_name: Roberto full_name: Sacco, Roberto id: 42C9F57E-F248-11E8-B48F-1D18A9856A87 last_name: Sacco - first_name: Leo full_name: James, Leo last_name: James - first_name: Daniel full_name: Pinschewer, Daniel last_name: Pinschewer - first_name: Keiryn full_name: Bennett, Keiryn last_name: Bennett - first_name: Jörg full_name: Menche, Jörg last_name: Menche - first_name: Andreas full_name: Bergthaler, Andreas last_name: Bergthaler citation: ama: Khamina K, Lercher A, Caldera M, et al. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 2017;13(12). doi:10.1371/journal.ppat.1006758 apa: Khamina, K., Lercher, A., Caldera, M., Schliehe, C., Vilagos, B., Sahin, M., … Bergthaler, A. (2017). Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. Public Library of Science. https://doi.org/10.1371/journal.ppat.1006758 chicago: Khamina, Kseniya, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, et al. “Characterization of Host Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens. Public Library of Science, 2017. https://doi.org/10.1371/journal.ppat.1006758. ieee: K. Khamina et al., “Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein,” PLoS Pathogens, vol. 13, no. 12. Public Library of Science, 2017. ista: Khamina K, Lercher A, Caldera M, Schliehe C, Vilagos B, Sahin M, Kosack L, Bhattacharya A, Májek P, Stukalov A, Sacco R, James L, Pinschewer D, Bennett K, Menche J, Bergthaler A. 2017. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 13(12), e1006758. mla: Khamina, Kseniya, et al. “Characterization of Host Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens, vol. 13, no. 12, e1006758, Public Library of Science, 2017, doi:10.1371/journal.ppat.1006758. short: K. Khamina, A. Lercher, M. Caldera, C. Schliehe, B. Vilagos, M. Sahin, L. Kosack, A. Bhattacharya, P. Májek, A. Stukalov, R. Sacco, L. James, D. Pinschewer, K. Bennett, J. Menche, A. Bergthaler, PLoS Pathogens 13 (2017). date_created: 2018-12-11T11:47:03Z date_published: 2017-12-01T00:00:00Z date_updated: 2021-01-12T08:01:48Z day: '01' ddc: - '576' - '616' department: - _id: GaNo doi: 10.1371/journal.ppat.1006758 file: - access_level: open_access checksum: 1aa20f19a1e90664fadce6e7d5284fdc content_type: application/pdf creator: system date_created: 2018-12-12T10:12:26Z date_updated: 2020-07-14T12:46:44Z file_id: '4944' file_name: IST-2018-931-v1+1_journal.ppat.1006758.pdf file_size: 4106772 relation: main_file file_date_updated: 2020-07-14T12:46:44Z has_accepted_license: '1' intvolume: ' 13' issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version publication: PLoS Pathogens publication_identifier: issn: - '15537366' publication_status: published publisher: Public Library of Science publist_id: '7276' pubrep_id: '931' quality_controlled: '1' scopus_import: 1 status: public title: Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2017' ... --- _id: '623' abstract: - lang: eng text: Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology. alternative_title: - ADVSANAT author: - first_name: Elisa full_name: Hill Yardin, Elisa last_name: Hill Yardin - first_name: Sonja full_name: Mckeown, Sonja last_name: Mckeown - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Andreas full_name: Grabrucker, Andreas last_name: Grabrucker citation: ama: 'Hill Yardin E, Mckeown S, Novarino G, Grabrucker A. Extracerebral dysfunction in animal models of autism spectrum disorder. In: Schmeisser M, Boekers T, eds. Translational Anatomy and Cell Biology of Autism Spectrum Disorder. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer; 2017:159-187. doi:10.1007/978-3-319-52498-6_9' apa: Hill Yardin, E., Mckeown, S., Novarino, G., & Grabrucker, A. (2017). Extracerebral dysfunction in animal models of autism spectrum disorder. In M. Schmeisser & T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder (Vol. 224, pp. 159–187). Springer. https://doi.org/10.1007/978-3-319-52498-6_9 chicago: Hill Yardin, Elisa, Sonja Mckeown, Gaia Novarino, and Andreas Grabrucker. “Extracerebral Dysfunction in Animal Models of Autism Spectrum Disorder.” In Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, 224:159–87. Advances in Anatomy Embryology and Cell Biology. Springer, 2017. https://doi.org/10.1007/978-3-319-52498-6_9. ieee: E. Hill Yardin, S. Mckeown, G. Novarino, and A. Grabrucker, “Extracerebral dysfunction in animal models of autism spectrum disorder,” in Translational Anatomy and Cell Biology of Autism Spectrum Disorder, vol. 224, M. Schmeisser and T. Boekers, Eds. Springer, 2017, pp. 159–187. ista: 'Hill Yardin E, Mckeown S, Novarino G, Grabrucker A. 2017.Extracerebral dysfunction in animal models of autism spectrum disorder. In: Translational Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 159–187.' mla: Hill Yardin, Elisa, et al. “Extracerebral Dysfunction in Animal Models of Autism Spectrum Disorder.” Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, vol. 224, Springer, 2017, pp. 159–87, doi:10.1007/978-3-319-52498-6_9. short: E. Hill Yardin, S. Mckeown, G. Novarino, A. Grabrucker, in:, M. Schmeisser, T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder, Springer, 2017, pp. 159–187. date_created: 2018-12-11T11:47:33Z date_published: 2017-05-28T00:00:00Z date_updated: 2021-01-12T08:06:46Z day: '28' department: - _id: GaNo doi: 10.1007/978-3-319-52498-6_9 editor: - first_name: Michael full_name: Schmeisser, Michael last_name: Schmeisser - first_name: Tobias full_name: Boekers, Tobias last_name: Boekers intvolume: ' 224' language: - iso: eng month: '05' oa_version: None page: 159 - 187 publication: Translational Anatomy and Cell Biology of Autism Spectrum Disorder publication_identifier: isbn: - 978-3-319-52496-2 issn: - '03015556' publication_status: published publisher: Springer publist_id: '7177' quality_controlled: '1' scopus_import: 1 series_title: Advances in Anatomy Embryology and Cell Biology status: public title: Extracerebral dysfunction in animal models of autism spectrum disorder type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 224 year: '2017' ...