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POSTER 57 - IMPROVING AXIS DEFECTS: A SUPPRESSOR OF BRACHYURY (SuB) ON MOUSE CHROMOSOME 6
Prof Karen Artzt
University of Texas at Austin
Institute for Cellular and Molecular Biology
Section of Molecular Genetics and Microbiology; A4800
Austin 78712-1064 USA
Artzt@uts.cc.utexas.edu
Co-Authors: Wu J, Centilli M, Vasquez G, Young S, Scolnick J, Spearow JL
Institution: University of Texas at Austin Institute for Cellular and Molecular
Biology, University of California at Davis
During a microsatellite genome scan to map tint (T/t tail interaction factor), we discovered a new hypomorphic gene that suppresses the Brachyury (T)phenotype. Homozygotes for the T/T die of serious axis defects on E10.5 while heterozygotes have a short tail. Double heterozygosity for both T and SuB have normal tails. To our knowledge, this is the first gene that improves axis defects and therefore may be relevant to spina bifida.
The origin for Sub is a spretus subline that was used in our intercross (Spr/Jls-RP): F1 mice were wild type at the T locus and heterozygous for tint versus spretus. Since all the F1s were normal tailed, to monitor the transmission of tint, it was necessary to testcross to T/+, +/+. We expected 1/2 normal tails, 1/4 shorts (T/+, spretus/+) and 1/4 tailless (T/+, tint/+) offspring. The normal tails would be of two indistinguishable genotypes and were discarded. In 713 testcross progeny, instead of the expected 2:1:1 ratio, we found a 2.5:1:0.5 ratio. When markers on chromosome 6 were typed, virtually all the tailless mice were of the tint type. The exceptions were recombinants for neighboring markers. The data map SuB to spretus chromosome 6 at 35.22 cM inseparable from D6Mit22 but distinct from D6Mit386. When T/+ was crossed to the input spretus stock, in the absence of any interaction, half the progeny are expected to be short tailed. The fact that 59/59 progeny had normal tails argues that we identified a suppressor of T.
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