Cell death serves as a single etiological cause of a wide spectrum of congenital urinary tract defects

Qiusha Guo, Piyush Tripathi, Edward Poyo, Yinqiu Wang, Paul F. Austin, Carlton M. Bates, Feng Chen

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Purpose: 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. Materials and 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;ROSADTA/+) 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.

Original languageEnglish
Pages (from-to)2320-2328
Number of pages9
JournalJournal of Urology
Volume185
Issue number6
DOIs
StatePublished - Jun 1 2011

Keywords

  • congenital abnormalities
  • diphtheria toxin
  • mesoderm
  • urogenital abnormalities
  • wolffian ducts

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