title: Cell death serves as a single etiological cause of a wide spectrum of congenital urinary tract defects.
abstract: OBJECTIVE
  We genetically disrupted the wolffian duct in mice to study the affected organogenesis processes and to test the hypothesis that cell loss can be the developmental basis for a wide spectrum of congenital anomalies in the kidney and urinary tract.
  
  
  METHODS
  We used Hoxb7-Cre transgenic lines (HC1 and HC2) to induce diphtheria toxin production from a ROSA(DTA) allele, disrupting the wolffian duct and derivatives.
  
  
  RESULTS
  The first set of mutants (HC1;ROSA(DTA/+)) exhibited agenesis of the kidney, ureter and reproductive tracts. The second set of mutants (HC2;ROSA(DTA/+)) exhibited diverse defects, including renal agenesis/hypoplasia, hydronephrosis, hydroureter, ureter-vas deferens fistulas in males and ureter-oviduct/uterus fistulas in females. The phenotypic differences correspond to the degree of apoptosis induced caudal truncation of the wolffian duct, which is less severe and more variable in HC2;ROSA(DTA/+) mice. Whenever the wolffian duct failed to reach the urogenital sinus, the ureter failed to separate from the wolffian duct, suggesting that ureteral migration along the common nephric duct to the cloaca and the subsequent common nephric duct degeneration constitute the only pathway for separating the ureter and wolffian duct derivatives.
  
  
  CONCLUSIONS
  The diverse and severe defects observed emphasize the central role of the wolffian duct in providing progenitors and signals for urogenital development. These results also indicate that the quantitative difference in cell death induced caudal truncation of the wolffian duct can lead to a wide range of qualitatively distinct defects, and that cell death can serve as a single etiological cause of a wide spectrum of congenital kidney and urinary tract defects.
authors.affiliation: Department of Internal Medicine/Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Qiusha
authors.initials: Q
authors.lastname: Guo
authors.forename: Piyush
authors.initials: P
authors.lastname: Tripathi
authors.forename: Edward
authors.initials: E
authors.lastname: Poyo
authors.forename: Yinqiu
authors.initials: Y
authors.lastname: Wang
authors.forename: Paul F
authors.initials: PF
authors.lastname: Austin
authors.forename: Carlton M
authors.initials: CM
authors.lastname: Bates
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D005260:Female; D007668:Kidney / Q000002:abnormalities; D008297:Male; D051379:Mice; D014551:Urinary Tract / Q000002:abnormalities*; D014928:Wolffian Ducts / Q000002:abnormalities