title: Age related expression of Werner's syndrome protein in selected tissues and coexpression of transcription factors.
abstract: OBJECTIVE
  Werner's syndrome (WS) is an uncommon autosomal recessive disease resulting from mutational inactivation of human WRN helicase, Werner's syndrome protein (WRNp). Patients with WS progressively develop a variety of aging characteristics after puberty. The aim of this study was to determine the distribution of WRNp and the expression of the transcription factors regulating WRN gene expression in a variety of human organs in an attempt to understand the WS phenotype.
  
  
  METHODS
  Tissue specimens were obtained from 16 controls aged from 27 gestational weeks to 70 years of age and a 56 year old female patient with WS. The distribution of WRNp and the expression of the transcription factors regulating WRN gene expression-SP1, AP2, and retinoblastoma protein (Rb)- were studied in the various human organs by immunohistochemical and immunoblot analyses.
  
  
  RESULTS
  In the healthy controls after puberty, high expression of WRNp was detected in seminiferous epithelial cells and Leydig cells in the testis, glandular acini in the pancreas, and the zona fasciculata and zona reticularis in the adrenal cortex. In addition, the SP1 and AP2 transcription factors, which regulate WRNp gene expression, appeared in an age dependent manner in those regions where WRNp was expressed. In controls after puberty, SP1 was expressed in the testis and adrenal gland, whereas AP2 was expressed in the pancreas.
  
  
  CONCLUSIONS
  These findings suggest that the age specific onset of WS may be related to age dependent expression of WRNp in specific organs.
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. motonaga@ncnp.go.jp
authors.forename: K
authors.initials: K
authors.lastname: Motonaga
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Hachiya
authors.forename: A
authors.initials: A
authors.lastname: Endo
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Ishikura
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Takashima
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000293:Adolescent; D000302:Adrenal Cortex / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005090:Exodeoxyribonucleases; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D053484:RecQ Helicases; D012671:Seminiferous Tubules / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D014898:Werner Syndrome / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
chemical_list: D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase