title: Anatomical studies of the fibroblast growth factor-10 mutant, Sonic Hedge Hog mutant and androgen receptor mutant mouse genital tubercle.
abstract: OBJECTIVE
  Congenital genital abnormalities have a diverse spectrum from hypospadias to cloacal anomalies. The molecular events in the normal and abnormal development of the genital tubercle (GT) are still obscure. Genetically engineered mice with specific gene deletions that affect genital anatomy are a useful tool to better understand the etiology of genital abnormalities. In this study, we compared the genital tubercle anatomy of the androgen receptor (AR) deficient, fibroblastic growth factor (FGF)-10 deficient and Sonic HedgeHog (Shh) deficient mutant male mice to that of the wild type male and female mouse.
  
  
  METHODS
  The lower pelvis of the androgen receptor deficient, FGF-10 deficient, Shh deficient mutant male and wild type male and female mouse at different gestational days (E13-21) and post natal ages (1 day-1 week) were studied. GTs were imaged, serially sectioned and stained immunohistochemically with antibodies raised against E-Cadherin, Cytokeratin 7, 10 and 14. Serial sections of the GTs were selected and three-dimensional computerized images were created to better elucidate the anatomy.
  
  
  RESULTS
  AR deficient mutant male mouse revealed a distinctive GT anatomy, different from both sexes. The corporal bodies and glans remained hypoplastic whereas the urethral spongiosa was more developed than the wild type female counterpart. This finding is consistent with the AR mutant mouse being a unique morphologic phenotype distinct from the normal male and female. FGF-10 deficient mutant male mouse revealed normal corporal bodies with failure of the urethral plate to fuse ventrally consistent with hypospadias. The Shh deficient mutant mouse demonstrated complete agenesis of GT outgrowth and a persistent cloaca.
  
  
  CONCLUSIONS
  Animal models bred by gene knockout technology or natural occurring mutants contribute to the basic understanding of normal and abnormal GT development. The anatomy of the these three mutant mice confirms the importance of the androgen receptor, FGF-10 and Shh in genital development.
authors.affiliation: Department of Urology, University of California, San Francisco, CA 94143-0738, USA.
authors.forename: Selcuk
authors.initials: S
authors.lastname: Yucel
authors.forename: Wenhui
authors.initials: W
authors.lastname: Liu
authors.forename: Dwight
authors.initials: D
authors.lastname: Cordero
authors.forename: Anne
authors.initials: A
authors.lastname: Donjacour
authors.forename: Gerald
authors.initials: G
authors.lastname: Cunha
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Baskin
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics*; D005865:Gestational Age; D053823:Hedgehog Proteins; D006801:Humans; D007021:Hypospadias / Q000453:epidemiology / Q000235:genetics*; D007633:Keratins / Q000032:analysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009154:Mutation; D011944:Receptors, Androgen / Q000172:deficiency / Q000235:genetics*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics*
chemical_list: C496463:FGF10 protein, human; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D053823:Hedgehog Proteins; D011944:Receptors, Androgen; C509239:SHH protein, human; D015534:Trans-Activators; D005346:Fibroblast Growth Factors; D007633:Keratins