{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:21:21Z","timestamp":1768519281631,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,28]]},"group-title":"Molecular Biology","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>\n                    In USA, six million individuals with Sub-Saharan ancestry carry two\n                    <jats:italic>APOL1<\/jats:italic>\n                    high-risk variants, which increase the risk for kidney diseases. Whether APOL1 high-risk variants are independent risk factors for cardiovascular diseases is unclear and requires further investigation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We characterized a mouse model to investigate the role of APOL1 in dyslipidemia and cardiovascular diseases. Transgenic mice carrying APOL1 (G0 and G1 variants) on bacterial artificial chromosomes (BAC\/APOL1 mice) were crossed with the ApoE knock-out (ApoE-KO) atherosclerosis mouse model. The compound transgenic mice were evaluated for the impact of APOL1 on systemic phenotypes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    ApoE-KO mice carrying APOL1-G0 and APOL1-G1 did not show differences in the extent of atherosclerotic lesions or aortic calcification, as evaluated by Sudan IV staining and radiographic examination, respectively. However, \u223c20% of ApoE-KO; BAC\/APOL1-G1 mice developed hydrocephalus and required euthanasia. The hydrocephalus was communicating and likely was due to excess cerebrospinal fluid produced by the choroid plexus, where epithelial cells expressed APOL1. Single-nuclear RNA-seq of choroid plexus identified solute transporter upregulation and mTORC2 pathway activation in APOL1-G1-expressing epithelial cells. Further, in the All of Us cohort, we found higher hydrocephalus prevalence among individuals with the\n                    <jats:italic>APOL1-G1<\/jats:italic>\n                    variant in both recessive and dominant models, supporting the mouse findings.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>While APOL1-G1 expression in ApoE-KO mice did not worsen cardiovascular disease phenotypes, we uncovered hydrocephalus as a novel APOL1 risk allele-mediated phenotype. These findings extend the spectrum of APOL1-associated pathologies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.12.28.630625","type":"posted-content","created":{"date-parts":[[2024,12,29]],"date-time":"2024-12-29T02:35:12Z","timestamp":1735439712000},"source":"Crossref","is-referenced-by-count":0,"title":["Apolipoprotein-L1 G1 variant contributes to hydrocephalus but not to atherosclerosis in apolipoprotein-E knock-out mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2049-7347","authenticated-orcid":false,"given":"Teruhiko","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Hong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Ashida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zu","family":"Xi 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