eprintid: 10088184 rev_number: 27 eprint_status: archive userid: 608 dir: disk0/10/08/81/84 datestamp: 2020-05-29 09:20:13 lastmod: 2021-12-19 00:13:19 status_changed: 2020-05-29 09:20:13 type: article metadata_visibility: show creators_name: Pauws, E creators_name: Hoshino, A creators_name: Bentley, L creators_name: Prajapati, S creators_name: Keller, C creators_name: Hammond, P creators_name: Martinez-Barbera, J-P creators_name: Moore, GE creators_name: Stanier, P title: Tbx22(null) mice have a submucous cleft palate due to reduced palatal bone formation and also display ankyloglossia and choanal atresia phenotypes ispublished: pub divisions: UCL divisions: B02 divisions: D13 divisions: G22 keywords: phenotypecongenital abnormalitymutationchoanal atresiacleft palategenestissue membranemice, knockoutosteoblastsosteogenesispalatepalate, hardmicenosepersistencex-linked inheritancemental condensationankyloglossiasubmucous cleft of hard palatemesenchymeintramembranous bone formation note: # The Author 2009. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: Craniofacial defects involving the lip and/or palate are among the most common human birth defects. X-linked cleft palate and ankyloglossia results from loss-of-function mutations in the gene encoding the T-box transcription factor TBX22. Further studies show that TBX22 mutations are also found in around 5% of non-syndromic cleft palate patients. Although palate defects are obvious at birth, the underlying developmental pathogenesis remains unclear. Here, we report a Tbx22null mouse, which has a submucous cleft palate (SMCP) and ankyloglossia, similar to the human phenotype, with a small minority showing overt clefts. We also find persistent oro-nasal membranes or, in some mice a partial rupture, resulting in choanal atresia. Each of these defects can cause severe breathing and/or feeding difficulties in the newborn pups, which results in ∼50% post-natal lethality. Analysis of the craniofacial skeleton demonstrates a marked reduction in bone formation in the posterior hard palate, resulting in the classic notch associated with SMCP. Our results suggest that Tbx22 plays an important role in the osteogenic patterning of the posterior hard palate. Ossification is severely reduced after condensation of the palatal mesenchyme, resulting from a delay in the maturation of osteoblasts. Rather than having a major role in palatal shelf closure, we show that Tbx22 is an important determinant for intramembranous bone formation in the posterior hard palate, which underpins normal palate development and function. These findings could have important implications for the molecular diagnosis in patients with isolated SMCP and/or unexplained choanal atresia. date: 2009-11-01 date_type: published publisher: OXFORD UNIV PRESS official_url: https://doi.org/10.1093/hmg/ddp368 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 130334 doi: 10.1093/hmg/ddp368 lyricists_name: Hammond, Peter lyricists_name: Martinez-Barbera, Juan lyricists_name: Moore, Gudrun lyricists_name: Pauws, Erwin lyricists_name: Stanier, Philip lyricists_id: PHAMM31 lyricists_id: JPMAR49 lyricists_id: GEMOO87 lyricists_id: EPAUW82 lyricists_id: PMSTA41 actors_name: Jayawardana, Anusha actors_id: AJAYA51 actors_role: owner full_text_status: public publication: Human Molecular Genetics volume: 18 number: 21 pagerange: 4171-4179 pages: 9 issn: 1460-2083 citation: Pauws, E; Hoshino, A; Bentley, L; Prajapati, S; Keller, C; Hammond, P; Martinez-Barbera, J-P; ... Stanier, P; + view all <#> Pauws, E; Hoshino, A; Bentley, L; Prajapati, S; Keller, C; Hammond, P; Martinez-Barbera, J-P; Moore, GE; Stanier, P; - view fewer <#> (2009) Tbx22(null) mice have a submucous cleft palate due to reduced palatal bone formation and also display ankyloglossia and choanal atresia phenotypes. Human Molecular Genetics , 18 (21) pp. 4171-4179. 10.1093/hmg/ddp368 <https://doi.org/10.1093/hmg%2Fddp368>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10088184/1/Pauws_Tbx22null%20mice%20have%20a%20submucous%20cleft%20palate%20due%20to%20reduced%20palatal%20bone%20formation%20and%20also%20display%20ankyloglossia%20and%20choanal%20atresia%20phenotypes.pdf