A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues

C. Chase Bolt, Colleen M. Elso, Xiaochen Lu, Fuming Pan, Andreas Kispert, Lisa Stubbs

Research output: Contribution to journalArticlepeer-review


The vertebrate T-box transcription factor gene Tbx18 performs a vital role in development of multiple organ systems. Tbx18 insufficiency manifests as recessive phenotypes in the upper urinary system, cardiac venous pole, inner ear, and axial skeleton; homozygous null mutant animals die perinatally. Here, we report a new regulatory mutation of Tbx18, a reciprocal translocation breaking 78. kbp downstream of the gene. 12Gso homozygotes present urinary and vertebral defects very similar to those associated with Tbx18-null mutations, but 12Gso is clearly not a global null allele since homozygotes survive into adulthood. We show that 12Gso down-regulates Tbx18 expression in a manner that is both spatially- and temporally-specific; combined with other data, the mutation points particularly to the presence of an essential urogenital enhancer located near the translocation breakpoint site. In support of this hypothesis, we identify a distal enhancer element, ECR1, which is active in developing urogenital and other tissues; we propose that disruption of this element leads to premature loss of Tbx18 function in 12Gso mutant mice. These data reveal a long-range regulatory architecture extending far downstream of Tbx18, identify a novel and likely essential urogenital enhancer, and introduce a new tool for dissecting postnatal phenotypes associated with dysregulation of Tbx18.

Original languageEnglish (US)
Pages (from-to)483-493
Number of pages11
JournalDevelopmental Biology
Issue number2
StatePublished - Aug 15 2014


  • Chromosome translocation
  • Regulatory mutation
  • T-box transcription factor
  • Urogenital development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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