{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T03:57:43Z","timestamp":1767844663431,"version":"3.49.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Dev Biol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Several imprinted genes have been implicated in the process of placentation. The distal region of mouse chromosome 7 (Chr 7) contains at least ten imprinted genes, several of which are expressed from the maternal homologue in the placenta. The corresponding paternal alleles of these genes are silenced in <jats:italic>cis<\/jats:italic> by an incompletely understood mechanism involving the formation of a repressive nuclear compartment mediated by the long non-coding RNA <jats:italic>Kcnq1ot1<\/jats:italic> initiated from imprinting centre 2 (IC2). However, it is unknown whether some maternally expressed genes are silenced on the paternal homologue via a <jats:italic>Kcnq1ot1-<\/jats:italic>independent mechanism. We have previously reported that maternal inheritance of a large truncation of Chr7 encompassing the entire IC2-regulated domain (DelTel7 allele) leads to embryonic lethality at mid-gestation accompanied by severe placental abnormalities. <jats:italic>Kcnq1ot1<\/jats:italic> expression can be abolished on the paternal chromosome by deleting IC2 (IC2KO allele). When the IC2KO mutation is paternally inherited, epigenetic silencing is lost in the region and the DelTel7 lethality is rescued in compound heterozygotes, leading to viable DelTel7\/IC2KO mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Considering the important functions of several IC2-regulated genes in placentation, we set out to determine whether these DelTel7\/IC2KO rescued conceptuses develop normal placentae. We report no abnormalities with respect to the architecture and vasculature of the DelTel7\/IC2KO rescued placentae. Imprinted expression of several of the IC2-regulated genes critical to placentation is also faithfully recapitulated in DelTel7\/IC2KO placentae.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Taken together, our results demonstrate that all the distal chromosome 7 imprinted genes implicated in placental function are silenced by IC2 and <jats:italic>Kcnq1ot1<\/jats:italic> on the paternal allele. Furthermore, our results demonstrate that the methylated maternal IC2 is not required for the regulation of nearby genes. The results show the potential for fully rescuing <jats:italic>trans<\/jats:italic> placental abnormalities that are caused by imprinting defects.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-213x-10-50","type":"journal-article","created":{"date-parts":[[2010,5,12]],"date-time":"2010-05-12T06:13:59Z","timestamp":1273644839000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Rescue of placental phenotype in a mechanistic model of Beckwith-Wiedemann syndrome"],"prefix":"10.1186","volume":"10","author":[{"given":"Rosemary","family":"Oh-McGinnis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron B","family":"Bogutz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang Yun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,5,11]]},"reference":[{"key":"527_CR1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/nature05918","volume":"447","author":"W Reik","year":"2007","unstructured":"Reik W: Stability and flexibility of epigenetic gene regulation in mammalian development. 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