{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T14:21:40Z","timestamp":1781446900638,"version":"3.54.1"},"reference-count":84,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,8,15]]},"abstract":"<jats:p>Background: The human chromosome 19q13.32 is a gene rich region and has been associated with multiple phenotypes, including late onset Alzheimer\u2019s disease (LOAD) and other age-related conditions. Objective: Here we developed the first humanized mouse model that contains the entire TOMM40 and APOE genes with all intronic and intergenic sequences including the upstream and downstream regions. Thus, the mouse model carries the human TOMM40 and APOE genes and their intact regulatory sequences. Methods: We generated the APOE-TOMM40 humanized mouse model in which the entire mouse region was replaced with the human (h)APOE-TOMM40 loci including their upstream and downstream flanking regulatory sequences using recombineering technologies. We then measured the expression of the human TOMM40 and APOE genes in the mice brain, liver, and spleen tissues using TaqMan based mRNA expression assays. Results: We investigated the effects of the \u2018523\u2019 polyT genotype (S\/S or VL\/VL), sex, and age on the human TOMM40- and APOE-mRNAs expression levels using our new humanized mouse model. The analysis revealed tissue specific and shared effects of the \u2018523\u2019 polyT genotype, sex, and age on the regulation of the human TOMM40 and APOE genes. Noteworthy, the regulatory effect of the \u2018523\u2019 polyT genotype was observed for all studied organs. Conclusion: The model offers new opportunities for basic science, translational, and preclinical drug discovery studies focused on the APOE genomic region in relation to LOAD and other conditions in adulthood.<\/jats:p>","DOI":"10.3233\/jad-230451","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T11:42:40Z","timestamp":1689334960000},"page":"1563-1576","source":"Crossref","is-referenced-by-count":2,"title":["The APOE-TOMM40 Humanized Mouse Model: Characterization of Age, Sex, and PolyT Variant Effects on Gene Expression"],"prefix":"10.1177","volume":"94","author":[{"given":"William K","family":"Gottschalk","sequence":"first","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Mahon","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dellila","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA"},{"name":"Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Barrera","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA"},{"name":"Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delaney","family":"Hill","sequence":"additional","affiliation":[{"name":"Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA"},{"name":"Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA"},{"name":"Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA"},{"name":"Center 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