{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:31:47Z","timestamp":1790829107395,"version":"4.1.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T00:00:00Z","timestamp":1389139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0083104","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T21:33:36Z","timestamp":1389216816000},"page":"e83104","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["NPPB and ACAN, Two Novel SHOX2 Transcription Targets Implicated in Skeletal Development"],"prefix":"10.1371","volume":"9","author":[{"given":"Miriam","family":"Aza-Carmona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Barca-Tierno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Hisado-Oliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberta","family":"Belinch\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Gorbenko-del Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Ignacio","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Benito-Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Campos-Barros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Heath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,1,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/ng0597-54","article-title":"Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome","volume":"16","author":"E Rao","year":"1997","journal-title":"Nat Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/ng0198-67","article-title":"SHOX mutations in dyschondrosteosis (Leri-Weill syndrome)","volume":"19","author":"V Belin","year":"1998","journal-title":"Nat Genet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng0198-70","article-title":"Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis","volume":"19","author":"DJ Shears","year":"1998","journal-title":"Nat Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1086\/449313","article-title":"A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis","volume":"77","author":"S Benito-Sanz","year":"2005","journal-title":"Am J Hum Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/ajmg.a.31676","article-title":"Compound heterozygosity of SHOX-encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD)","volume":"143","author":"A Campos-Barros","year":"2007","journal-title":"Am J Med Genet A"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1399-0004.2007.00875.x","article-title":"The homozygous deletion of the 3\u2032 enhancer of the SHOX gene causes Langer mesomelic dysplasia","volume":"72","author":"R Bertorelli","year":"2007","journal-title":"Clin Genet"},{"issue":"2","key":"ref7","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1210\/jc.2010-1689","article-title":"Clinical and molecular evaluation of SHOX\/PAR1 duplications in Leri-Weill dyschondrosteosis (LWD) and idiopathic short stature (ISS)","volume":"96","author":"S Benito-Sanz","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"ref8","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/ejhg.2011.210","article-title":"Identification of the first PAR1 deletion encompassing upstream SHOX enhancers in a family with idiopathic short stature","volume":"20","author":"S Benito-Sanz","year":"2012","journal-title":"Eur J Hum Genet"},{"issue":"7","key":"ref9","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1136\/jmedgenet-2011-100678","article-title":"Identification of the first recurrent PAR1 deletion in L\u00e9ri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer","volume":"49","author":"S Benito-Sanz","year":"2012","journal-title":"J Med Genet"},{"issue":"6 Suppl","key":"ref10","first-page":"7","article-title":"Epidemiology of SHOX deficiency","volume":"33","author":"A Nicolosi","year":"2011","journal-title":"J Endocrinol Invest"},{"issue":"5","key":"ref11","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1073\/pnas.95.5.2406","article-title":"SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain, heart, and limb development","volume":"95","author":"RJ Blaschke","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1093\/hmg\/ddm266","article-title":"BNP is a transcriptional target of the short stature homeobox gene SHOX","volume":"16","author":"A Marchini","year":"2007","journal-title":"Hum Mol Genet"},{"issue":"8","key":"ref13","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1093\/hmg\/ddr030","article-title":"FGFR3 is a target of the homeobox transcription factor SHOX in limb development","volume":"20","author":"E Decker","year":"2011","journal-title":"Hum Mol Genet"},{"issue":"8","key":"ref14","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/hmg\/ddr032","article-title":"SHOX interacts with the chondrogenic transcription factors SOX5 and SOX6 to activate the aggrecan enhancer","volume":"20","author":"M Aza-Carmona","year":"2011","journal-title":"Hum Mol Genet"},{"issue":"7045","key":"ref15","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/nature03648","article-title":"Early developmental arrest of mammalian limbs lacking HoxA\/HoxD gene function","volume":"435","author":"M Kmita","year":"2005","journal-title":"Nature"},{"issue":"9","key":"ref16","doi-asserted-by":"crossref","first-page":"e45369","DOI":"10.1371\/journal.pone.0045369","article-title":"The homeobox transcription factor HOXA9 is a regulator of SHOX in U2OS cells and chicken micromass cultures","volume":"7","author":"C Durand","year":"2012","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1093\/hmg\/9.5.695","article-title":"The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome","volume":"9","author":"M Clement-Jones","year":"2000","journal-title":"Hum Mol Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.ydbio.2006.07.008","article-title":"Expression of the short stature homeobox gene Shox is restricted by proximal and distal signals in chick limb buds and affects the length of skeletal elements","volume":"298","author":"E Tiecke","year":"2006","journal-title":"Dev Biol"},{"issue":"8","key":"ref19","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1210\/jc.2003-032230","article-title":"Expression of SHOX in human fetal and childhood growth plate","volume":"89","author":"CJ Munns","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"19","key":"ref20","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1242\/dev.02013","article-title":"Shox2-deficient mice exhibit a rare type of incomplete clefting of the secondary palate","volume":"132","author":"L Yu","year":"2005","journal-title":"Development"},{"issue":"14","key":"ref21","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1161\/CIRCULATIONAHA.106.637819","article-title":"Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development","volume":"115","author":"RJ Blaschke","year":"2007","journal-title":"Circulation"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ydbio.2008.12.028","article-title":"Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5","volume":"327","author":"RA Espinoza-Lewis","year":"2009","journal-title":"Dev Biol"},{"issue":"23","key":"ref23","doi-asserted-by":"crossref","first-page":"4625","DOI":"10.1093\/hmg\/ddq393","article-title":"Shox2 mediates Tbx5 activity by regulating Bmp4 in the pacemaker region of the developing heart","volume":"19","author":"S Puskaric","year":"2010","journal-title":"Hum Mol Genet"},{"issue":"2","key":"ref24","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ydbio.2011.05.663","article-title":"Ectopic expression of Nkx2.5 suppresses the formation of the sinoatrial node in mice","volume":"356","author":"RA Espinoza-Lewis","year":"2011","journal-title":"Dev Biol"},{"issue":"12","key":"ref25","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1073\/pnas.0510544103","article-title":"A mouse model for human short-stature syndromes identifies Shox2 as an upstream regulator of Runx2 during long-bone development","volume":"103","author":"J Cobb","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"24","key":"ref26","doi-asserted-by":"crossref","first-page":"6071","DOI":"10.1242\/jcs.111997","article-title":"Shox2 regulates progression through chondrogenesis in the mouse proximal limb","volume":"125","author":"BE Bobick","year":"2012","journal-title":"J Cell Sci"},{"issue":"2","key":"ref27","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.ydbio.2007.03.518","article-title":"Shox2 is required for chondrocyte proliferation and maturation in proximal limb skeleton","volume":"306","author":"L Yu","year":"2007","journal-title":"Dev Biol"},{"issue":"19","key":"ref28","doi-asserted-by":"crossref","first-page":"17029","DOI":"10.1074\/jbc.M111.234252","article-title":"Functional redundancy between human SHOX and mouse Shox2 genes in the regulation of sinoatrial node formation and pacemaking function","volume":"286","author":"H Liu","year":"2011","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1128\/MCB.00695-08","article-title":"L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream enhancer","volume":"28","author":"Y Han","year":"2008","journal-title":"Mol Cell Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1093\/hmg\/10.26.3083","article-title":"The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator","volume":"10","author":"E Rao","year":"2001","journal-title":"Hum Mol Genet"},{"key":"ref31","unstructured":"Sobradillo B, Aguirre A, Aresti U, Bilbao A, Fern\u00e1ndez-Ramos C, <etal>et al<\/etal>.. (2002) Curvas y Tablas de crecimiento (Estudios Longitudinal y Transversal). In: Fundaci\u00f3n Faustino Orbegozo Eizaguirre Bilbao. pp. 1\u201336."},{"key":"ref32","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1086\/506390","article-title":"Characterization of SHOX deletions in Leri-Weill dyschondrosteosis (LWD) reveals genetic heterogeneity and no recombination hotspots","volume":"79","author":"S Benito-Sanz","year":"2006","journal-title":"Am J Hum Genet"},{"issue":"10","key":"ref33","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/humu.9456","article-title":"PAR1 deletions downstream of SHOX are the most frequent defect in a Spanish cohort of L\u00e9ri-Weill dyschondrosteosis (LWD) probands","volume":"27","author":"S Benito-Sanz","year":"2006","journal-title":"Hum Mutat"},{"key":"ref34","first-page":"154","article-title":"A simple, efficient method for the separate isolation of RNA and DNA from the same cells","volume":"8","author":"NC Nicolaides","year":"1990","journal-title":"Biotechniques"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1534-5807(01)00003-X","article-title":"The transcription factors L-Sox5 and Sox6 are essential for cartilage formation","volume":"1","author":"P Smits","year":"2001","journal-title":"Dev Cell"},{"issue":"11","key":"ref36","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1101\/gad.7.11.2120","article-title":"Cooperative dimerization of paired class homeo domains on DNA","volume":"7","author":"D Wilson","year":"1993","journal-title":"Genes Dev"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/humu.20187","article-title":"Alteration of DNA binding, dimerization, and nuclear translocation of SHOX homeodomain mutations identified in idiopathic short stature and Leri-Weill Dyschondrosteosis","volume":"26","author":"KU Schneider","year":"2005","journal-title":"Hum Mut"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1053\/joca.2001.0447","article-title":"L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway","volume":"9 Suppl A","author":"V Lefebvre","year":"2001","journal-title":"Osteoarthritis Cartilage"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1136\/jmg.2006.040998","article-title":"High incidence of SHOX anomalies in individuals with short stature","volume":"43","author":"C Huber","year":"2006","journal-title":"J Med Genet"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1136\/jmg.2009.067785","article-title":"Enhancer mutations of the SHOX gene as a frequent cause of short stature \u2013 the essential role of a 250 kb downstream regulatory domain","volume":"46","author":"J Chen","year":"2009","journal-title":"J Med Genet"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1073\/pnas.95.5.2337","article-title":"Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide","volume":"95","author":"M Suda","year":"1998","journal-title":"Proc Natl Acad Sci"},{"issue":"9","key":"ref42","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.ejheart.2008.07.014","article-title":"State of the art: using natriuretic peptide levels in clinical practice","volume":"10","author":"A Maisel","year":"2008","journal-title":"Eur J Heart Fail"},{"issue":"6","key":"ref43","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1128\/MCB.15.6.3318","article-title":"Sequence-specific targeting of nuclear signal transduction pathways by homeodomain proteins","volume":"15","author":"DA Grueneberg","year":"1995","journal-title":"Mol Cell Biol"},{"issue":"1","key":"ref44","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0959-440X(96)80096-0","article-title":"Homeodomain interactions","volume":"6","author":"C Wolberger","year":"1996","journal-title":"Curr Opin Struct Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1093\/nar\/gkl105","article-title":"The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors","volume":"34","author":"S Wissm\u00fcller","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"5234","key":"ref46","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1126\/science.270.5234.262","article-title":"Crystal structure of the MATal\/MATa2 homeodomain heterodimer bound to DNA","volume":"270","author":"T Li","year":"1995","journal-title":"Science"},{"issue":"2","key":"ref47","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/ajmg.10422","article-title":"Complete SHOX deficiency causes Langer mesomelic dysplasia","volume":"110","author":"AR Zinn","year":"2002","journal-title":"Am J Med Genet"},{"issue":"3","key":"ref48","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/hmg\/7.3.415","article-title":"A new human homeobox gene OGI2X is a member of the most conserved homeobox gene family and is expressed during heart development in mouse","volume":"7","author":"EV Semina","year":"1998","journal-title":"Hum Mol Genet"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0083104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T20:09:10Z","timestamp":1588968550000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0083104"}},"subtitle":[],"editor":[{"given":"Andre","family":"van Wijnen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,1,8]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0083104","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,8]]}}}