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http://purl.uniprot.org/citations/19412548http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19412548http://www.w3.org/2000/01/rdf-schema#comment"Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B(-/-) mice. While Pds5A(-/-) and Pds5B(-/-) mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A(-/-) or Pds5B(-/-) mice. We further identified a functional missense mutation (R1292Q) in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0005232"xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Chang J."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Fu M."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Huang J."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Jain S."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Milbrandt J."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Zhang B."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Kulkarni S."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Deardorff M.A."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Dorsett D."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Heuckeroth R.O."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Krantz I."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Kashyap R."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Jay P.Y."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Beebe D.C."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Uzielli M.L."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Salavaggione E."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/author"Shashikant K."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/pages"e5232"xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/title"Dosage effects of cohesin regulatory factor PDS5 on mammalian development: implications for cohesinopathies."xsd:string
http://purl.uniprot.org/citations/19412548http://purl.uniprot.org/core/volume"4"xsd:string
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