| First Author | Zachgo J | Year | 1998 |
| Journal | Dev Genet | Volume | 23 |
| Issue | 1 | Pages | 86-96 |
| PubMed ID | 9706697 | Mgi Jnum | J:49126 |
| Mgi Id | MGI:1276696 | Doi | 10.1002/(SICI)1520-6408(1998)23:1<86::AID-DVG9>3.0.CO;2-2 |
| Citation | Zachgo J, et al. (1998) Genetic interactions suggest that Danforth's short tail (Sd) is a gain-of-function mutation. Dev Genet 23(1):86-96 |
| abstractText | Danforth's short tail (Sd) is a semidominant mutation on mouse chromosome 2 that acts cell autonomously in the notochord and leads io iis disintegration, and thus causes severe defects in somite patterning and which is severely reduced or absent in Sd heterozygotes, is vertebral column development. The molecular nature of the Sd gene and mutation is unknown, and ii is unclear whether Sd is a loss-of-function mutation and the semidominant inheritance of the Sd phenotype is due io haploinsufficiency, or whether Sd represents a gain-of-function mutation in a gene essential for notochord development and maintenance. Here, we report on the genetic interaction between Sd and an insertional mutation called Etl4(lacZ), which provides genetic evidence that Sd is a gain-of-function mutation. Etl4(lacZ) is an enhancer trap insertion, which gives rise to lacZ expression in distinct cell types, including the notochord. In homozygosity, the lacZ insertion leads to abnormal vertebrae in the caudal part of the vertebral column. Etl4(lacZ) maps approximately 0.75 cM distal to Sd, and in double heterozygotes modifies the Sd phenotype contrarily, depending on the chromosomal configuration of the Sd and Etl4(lacZ) mutations. When Etl4(lacZ) is present on the chromosome wild type for Sd (Sd +/+ Etl4(lacZ); trans configuration), the Sd phenotype is enhanced, i.e., Vertebral malformations extend io more anterior positions and the vertebral body of the axis is further reduced. Conversely, when Etl4(lacZ) is present on the same chromosome as Sd (Sd Etl4(lacZ) /+ +; cis configuration), the Sd phenotype is attenuated, i.e., vertebral malformations are confined io more posterior levels, and the dens axis, restored. The different effect of the Etl4(lacZ) insertion on Sd, depending oil iis presence in trans or cis, suggests a direct interaction of the transgene insertion with the Sd gene. Additionally, the attenuation of;he Sd phenotype by Etl4(lacZ) in cis suggests that Sd is a gain-of-function mutation and lends support to the idea that Etl4(lacZ) is a new allele of Sd. (C) 1998 Wiley-Liss, Inc. |
