{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:56:43Z","timestamp":1790081803267,"version":"4.0.1"},"reference-count":52,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":3059,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title><jats:p>The ZIC transcription factors are key mediators of embryonic development and ZIC3 is the gene most commonly associated with situs defects (heterotaxy) in humans. Half of patient ZIC3 mutations introduce a premature termination codon (PTC). In vivo, PTC-containing transcripts might be targeted for nonsense-mediated decay (NMD). NMD efficiency is known to vary greatly between transcripts, tissues and individuals and it is possible that differences in survival of PTC-containing transcripts partially explain the striking phenotypic variability that characterizes ZIC3-associated congenital defects. For example, the PTC-containing transcripts might encode a C-terminally truncated protein that retains partial function or that dominantly interferes with other ZIC family members. Here we describe the katun (Ka) mouse mutant, which harbours a mutation in the Zic3 gene that results in a PTC. At the time of axis formation there is no discernible decrease in this PTC-containing transcript in vivo, indicating that the mammalian Zic3 transcript is relatively insensitive to NMD, prompting the need to re-examine the molecular function of the truncated proteins predicted from human studies and to determine whether the N-terminal portion of ZIC3 possesses dominant-negative capabilities. A combination of in vitro studies and analysis of the Ka phenotype indicate it is a null allele of Zic3 and that the N-terminal portion of ZIC3 does not encode a dominant-negative molecule. Heterotaxy in patients with PTC-containing ZIC3 transcripts probably arises due to loss of ZIC3 function alone.<\/jats:p>","DOI":"10.1242\/dmm.011668","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T03:52:01Z","timestamp":1361505121000},"source":"Crossref","is-referenced-by-count":11,"title":["A murine<i>Zic3<\/i>transcript with a premature termination codon evades nonsense-mediated decay during axis formation"],"prefix":"10.1242","author":[{"given":"Jehangir N.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Australian National University, Canberra, ACT, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radiya G.","family":"Ali","sequence":"additional","affiliation":[{"name":"Australian National University, Canberra, ACT, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Warr","sequence":"additional","affiliation":[{"name":"Mammalian Genetics Unit, MRC Harwell, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Australian National University, Canberra, ACT, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Bellchambers","sequence":"additional","affiliation":[{"name":"Australian National University, Canberra, ACT, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen S.","family":"Barratt","sequence":"additional","affiliation":[{"name":"Australian National University, Canberra, ACT, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Australian National University, Canberra, ACT, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth M.","family":"Arkell","sequence":"additional","affiliation":[{"name":"Australian National University, Canberra, ACT, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2021042501094165600_b1-0060755","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.biocel.2012.08.012","article-title":"Zinc fingers of the cerebellum (Zic): transcription factors and co-factors","volume":"44","author":"Ali","year":"2012","journal-title":"Int. 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