title: Murine expression and mutation analyses of the prostate androgen-regulated mucin-like protein 1 (Parm1) gene, a candidate for human epispadias.
abstract: BACKGROUND
  Epispadias is the mildest phenotype of the human bladder exstrophy-epispadias complex (BEEC), and presents with varying degrees of severity. This urogenital birth defect results from a disturbance in the septation process, during which separate urogenital and anorectal components are formed through division of the cloaca. This process is reported to be influenced by androgen signaling. The human PARM1 gene encodes the prostate androgen-regulated mucin-like protein 1, which is expressed in heart, kidney, and placenta.
  
  
  METHODS
  We performed whole mount in situ hybridization analysis of Parm1 expression in mouse embryos between gestational days (GD) 9.5 and 12.5, which are equivalent to human gestational weeks 4-6. Since the spatio-temporal localization of Parm1 corresponded to tissues which are affected in human epispadias, we sequenced PARM1 in 24 affected patients.
  
  
  RESULTS
  We found Parm1 specifically expressed in the region of the developing cloaca, the umbilical cord, bladder anlage, and the urethral component of the genital tubercle. Additionally, Parm1 expression was detected in the muscle progenitor cells of the somites and head mesenchyme. PARM1 gene analysis revealed no alterations in the coding region of any of the investigated patients.
  
  
  CONCLUSIONS
  These findings suggest that PARM1 does not play a major role in the development of human epispadias. However, we cannot rule out the possibility that a larger sample size would enable detection of rare mutations in this gene.
authors: Department of Developmental Genetics, Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
authors: Lars
authors: L
authors: Wittler
authors: Alina
authors: A
authors: Hilger
authors: Judith
authors: J
authors: Proske
authors: Tracie
authors: T
authors: Pennimpede
authors: Markus
authors: M
authors: Draaken
authors: Anne-Karoline
authors: AK
authors: Ebert
authors: Wolfgang
authors: W
authors: Rösch
authors: Raimund
authors: R
authors: Stein
authors: Markus M
authors: MM
authors: Nöthen
authors: Heiko
authors: H
authors: Reutter
authors: Michael
authors: M
authors: Ludwig
mesh_terms: D000727:Androgen-Binding Protein / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D004252:DNA Mutational Analysis; D004842:Epispadias / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D010641:Phenotype; D011467:Prostate / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000727:Androgen-Binding Protein; C527680:PARM1 protein, human; C547510:Parm-1 protein, mouse