title: Mutation of murine Sox4 untranslated regions results in partially penetrant perinatal lethality.
abstract: BACKGROUND
  Sox4 is an essential gene, and genetic deletion results in embryonic lethality. In an effort to develop mice with tissue-specific deletion, we bred conditional knockout mice bearing LoxP recombination sites flanking the Sox4 gene, with the LoxP sites located in the Sox4 5'UTR and 3'UTR.
  
  
  RESULTS
  The number of mice homozygous for this LoxP-flanked conditional knockout allele was far below the expected number, suggesting embryonic lethality with reduced penetrance. From over 200 animals bred, only 11% were homozygous Sox4(flox/flox) mice, compared to the expected Mendelian ratio of 25% (p<0.001). Moreover, there was a significant reduction in the number of female Sox4(flox/flox) mice (26%) relative to male Sox4(flox/flox) mice (p=0.0371). Reduced Sox4 expression in homozygous embryos was confirmed by in-situ hybridization and Quantitative real-time polymerase chain reaction (QPCR).
  
  
  CONCLUSIONS
  LoxP sites in the 5' and 3' UTR of both alleles of Sox4 resulted in reduced, but variable expression of Sox4 message.
authors.affiliation: Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, U.S.A.
authors.forename: Walter Guy
authors.initials: WG
authors.lastname: Wiles
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, U.S.A.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Mou
authors.affiliation: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, U.S.A.
authors.forename: Yang
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, U.S.A.
authors.forename: Alyssa B
authors.initials: AB
authors.lastname: Long
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, U.S.A.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Scharer
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, U.S.A.
authors.forename: Birdal
authors.initials: B
authors.lastname: Bilir
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, U.S.A.
authors.forename: Demetri D
authors.initials: DD
authors.lastname: Spyropoulos
authors.affiliation: Cancer Research Program, The Methodist Hospital Research Institute, Houston, TX, U.S.A.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jenkins
authors.affiliation: Cancer Research Program, The Methodist Hospital Research Institute, Houston, TX, U.S.A.
authors.forename: Neal G
authors.initials: NG
authors.lastname: Copeland
authors.affiliation: Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, U.S.A. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, U.S.A.
authors.forename: W David
authors.initials: WD
authors.lastname: Martin
authors.affiliation: Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, U.S.A. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, U.S.A. cmoreno@emory.edu.
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Moreno
mesh_terms: D000818:Animals; D001947:Breeding; D002460:Cell Line; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D005804:Genes, Lethal; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D019683:Penetrance; D066087:Perinatal Death / Q000209:etiology*; D010641:Phenotype; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics*; D020506:Untranslated Regions
chemical_list: D012333:RNA, Messenger; D055751:SOXC Transcription Factors; D020506:Untranslated Regions
keywords: ISH; Mouse; Sox4; perinatal lethality; transcription