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Here, we show that\n                  <jats:italic>\n                    Pkhd1\n                    <jats:sup>del3-67\/del3-67<\/jats:sup>\n                  <\/jats:italic>\n                  mutant mice develop congenital glaucoma due to anterior segment dysgenesis. Using a combination of genetic, epigenetic, bioinformatics and mouse developmental biology approaches, we show that\n                  <jats:italic>\n                    Pkhd1\n                    <jats:sup>del3-67\/del3-67<\/jats:sup>\n                  <\/jats:italic>\n                  mice lack\n                  <jats:italic>Tfap2b<\/jats:italic>\n                  and AP-2\u03b2 expression in a subset of periocular mesenchymal cells at E13.5 and its derivatives. Our data suggest that the\n                  <jats:italic>\n                    Pkhd1\n                    <jats:sup>del3-67<\/jats:sup>\n                  <\/jats:italic>\n                  deletion disrupts features of the\n                  <jats:italic>Pkhd1-Tfap2b<\/jats:italic>\n                  genomic architecture essential for\n                  <jats:italic>Tfap2b<\/jats:italic>\n                  cell-specific activities. Consistent with this model,\n                  <jats:italic>\n                    Pkhd1\n                    <jats:sup>del3-67\/+<\/jats:sup>\n                    ;Tfap2b\n                    <jats:sup>ko\/+<\/jats:sup>\n                  <\/jats:italic>\n                  trans-heterozygotes lack\n                  <jats:italic>Tfap2b<\/jats:italic>\n                  and AP-2\u03b2 in relevant cell-types and have similar eye abnormalities as neural crest cell-specific\n                  <jats:italic>\n                    Tfap2b\n                    <jats:sup>ko<\/jats:sup>\n                  <\/jats:italic>\n                  mutants. These findings provide a likely causal explanation for how SNPs associated with\n                  <jats:italic>PKHD1<\/jats:italic>\n                  are functionally linked to POAG and add insight into understanding the complexity of disease-causing SNP associations and gene regulatory mechanisms.\n                <\/jats:p>","DOI":"10.64898\/2026.02.15.706040","type":"posted-content","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:10:16Z","timestamp":1771391416000},"source":"Crossref","is-referenced-by-count":1,"title":["Studies of mice with a large deletion of the ARPKD-associated\n                  <i>Pkhd1<\/i>\n                  locus likely explain its GWAS association with glaucoma in humans"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5773-8637","authenticated-orcid":false,"given":"Yu","family":"Ishimoto","sequence":"first","affiliation":[{"name":"Kidney Disease Branch; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis F","family":"Menezes","sequence":"additional","affiliation":[{"name":"Kidney Disease Branch; 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