| First Author | Bolt CC | Year | 2014 |
| Journal | Dev Biol | Volume | 392 |
| Issue | 2 | Pages | 483-93 |
| PubMed ID | 24854998 | Mgi Jnum | J:215002 |
| Mgi Id | MGI:5604340 | Doi | 10.1016/j.ydbio.2014.05.010 |
| Citation | Bolt CC, et al. (2014) A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues. Dev Biol 392(2):483-93 |
| abstractText | 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 78kbp 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. |
