{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:12:42Z","timestamp":1793945562575,"version":"4.8.0"},"reference-count":41,"publisher":"Cold Spring Harbor Laboratory","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2003,10,15]]},"abstract":"<jats:p>Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches. One such transcription factor, Arx, exhibits <jats:italic>Ngn3<\/jats:italic>-dependent expression throughout endocrine pancreas development in \u03b1, \u03b2-precursor, and \u03b4 cells. We have used gene targeting in mouse embryonic stem cells to generate <jats:italic>Arx<\/jats:italic> loss-of-function mice. <jats:italic>Arx<\/jats:italic>-deficient animals are born at the expected Mendelian frequency, but develop early-onset hypoglycemia, dehydration, and weakness, and die 2 d after birth. Immunohistological analysis of pancreas from <jats:italic>Arx<\/jats:italic> mutants reveals an early-onset loss of mature endocrine \u03b1 cells with a concomitant increase in \u03b2-and \u03b4-cell numbers, whereas islet morphology remains intact. Our study indicates a requirement of Arx for \u03b1-cell fate acquisition and a repressive action on \u03b2-and \u03b4-cell destiny, which is exactly the opposite of the action of Pax4 in endocrine commitment. Using multiplex reverse transcriptase PCR (RT-PCR), we demonstrate an accumulation of <jats:italic>Pax4<\/jats:italic> and <jats:italic>Arx<\/jats:italic> transcripts in <jats:italic>Arx<\/jats:italic> and <jats:italic>Pax4<\/jats:italic> mutant mice, respectively. We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts.<\/jats:p>","DOI":"10.1101\/gad.269003","type":"journal-article","created":{"date-parts":[[2003,10,15]],"date-time":"2003-10-15T17:18:26Z","timestamp":1066238306000},"page":"2591-2603","source":"Crossref","is-referenced-by-count":541,"title":["Opposing actions of Arx and Pax4 in endocrine pancreas development"],"prefix":"10.1101","volume":"17","author":[{"given":"Patrick","family":"Collombat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Mansouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Hecksher-S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palle","family":"Serup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Krull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Gradwohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gruss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2003,10,15]]},"reference":[{"key":"2021111519313136000_17.20.2591.1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01228136"},{"key":"2021111519313136000_17.20.2591.2","doi-asserted-by":"publisher","DOI":"10.1038\/385257a0"},{"key":"2021111519313136000_17.20.2591.3","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.12.1763"},{"key":"2021111519313136000_17.20.2591.4","doi-asserted-by":"publisher","DOI":"10.1038\/23716"},{"key":"2021111519313136000_17.20.2591.5","doi-asserted-by":"publisher","DOI":"10.1007\/s003350010141"},{"key":"2021111519313136000_17.20.2591.6","doi-asserted-by":"publisher","DOI":"10.1054\/npep.2001.0848"},{"key":"2021111519313136000_17.20.2591.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00324-X"},{"key":"2021111519313136000_17.20.2591.8","doi-asserted-by":"publisher","DOI":"10.1038\/nrg841"},{"key":"2021111519313136000_17.20.2591.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1607"},{"key":"2021111519313136000_17.20.2591.10","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1242\/dev.129.10.2447","volume":"129","year":"2002","journal-title":"Development"},{"key":"2021111519313136000_17.20.2591.11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1242\/dev.121.1.11","volume":"121","year":"1995","journal-title":"Development"},{"key":"2021111519313136000_17.20.2591.12","doi-asserted-by":"crossref","first-page":"19968","DOI":"10.1016\/S0021-9258(17)32115-4","volume":"269","year":"1994","journal-title":"J. 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